Trial Outcomes & Findings for To Compare the Effect of a Subcutaneous Canakinumab Administration to Placebo in Patients With Impaired Glucose Tolerance or Patients With Type 2 Diabetes With Differing Baseline Diabetes Therapies (NCT NCT01068860)

NCT ID: NCT01068860

Last Updated: 2011-09-05

Results Overview

Change in Insulin Secretion Rate stimulated by Liquid mixed-meal challenge. Blood samples were taken prior to and after meal for glucose and insulin at sample times: -20, -10, -1 and 10, 20, 30, 60, 90, 120, 180, and 240 minutes relative to the start of the meal.A mixed model with treatment fitted as fixed effect, and population and the interaction of population and treatment fitted as random effects were used for the comparison of Canakinumab versus placebo within each T2DM population. The mixed model did not include patients from the IGT population

• Recruitment status: COMPLETED
• Study phase: PHASE2
• Target enrollment: 246 participants
• Primary outcome timeframe: Baseline, 4 weeks
• Results posted on: 2011-09-05

Participant Flow

Qualified patients entered a 4-week run-in period while taking current therapy thru the study. After the run-in, patients had the baseline meal challenge. Then patients were randomized. A 2nd meal challenge was performed after 4 wks. This ended the study except for a follow up phone call after approx.90 days to record serious adverse events (SAEs)

Participant milestones

Measure	Canakinumab 150 mg + Metformin Eligible participants received a single subcutaneous injection Canakinumab 150 mg. Patients must have had documented diagnosis of Type 2 Diabetes Mellitus and be on a stable dose of Metformin (Met) monotherapy treatment at least 1000 mg/day for 3 months prior to screening	Placebo + Metformin Eligible participants received a single subcutaneous injection of Placebo to Canakinumab. Patients must have had documented diagnosis of Type 2 Diabetes Mellitus and be on a stable dose of Metformin (Met) monotherapy treatment at least 1000 mg/day for 3 months prior to screening	Canakinumab 150 mg + Metformin + Sulfonylurea Eligible participants received a single subcutaneous injection of Canakinumab 150 mg.Patients must have had documented diagnosis of Type 2 Diabetes Mellitus and be on a stable dose of Metformin (Met) at least 1000 mg/day , and a Sulfonylurea (Sulfonyl), at least 1/2 the maximally labeled dose combination therapy, for 3 months prior to screening.	Placebo + Metformin + Sulfonylurea Eligible participants received a single subcutaneous injection of Placebo to Canakinumab.Patients must have had documented diagnosis of Type 2 Diabetes Mellitus and be on a stable dose of Metformin (Met) at least 1000 mg/day , and a Sulfonylurea (Sulfonyl), at least 1/2 the maximally labeled dose combination therapy, for 3 months prior to screening.	Canakinumab 150 mg Canakinumab 150 mg + Met + Sulfonyl + Thia Eligible participants received a single subcutaneous injection of Canakinumab 150 mg.Patients must have had documented diagnosis of Type 2 Diabetes Mellitus and be on a stable dose of Metformin (Met) at least 1000 mg/day , and a Sulfonylurea (Sulfonyl), at least 1/2 the maximally labeled dose, and a Thiazolidinedione (Thiaz)at least 1/2 the maximally labeled dose combination therapy, for 3 months prior to screening.	Placebo + Met + Sulfonyl + Thiaz Eligible participants received a single subcutaneous injection of Placebo to Canakinumab. Patients must have had documented diagnosis of Type 2 Diabetes Mellitus and be on a stable dose of Metformin (Met) at least 1000 mg/day , and a Sulfonylurea (Sulfonyl), at least 1/2 the maximally labeled dose, and a Thiazolidinedione (Thiaz)at least 1/2 the maximally labeled dose combination therapy, for 3 months prior to screening.	Canakinumab 150 mg + Insulin Eligible participants received a single subcutaneous injection of Canakinumab 150 mg. Patients must have had documented diagnosis of Type 2 Diabetes Mellitus for 3 months prior to screening and be on a stable dose of Insulin, 2 insulin injections per day for a total daily dose of less than 100 U with or without Metformin (Met)for 3 months prior to screening	Placebo + Insulin Eligible participants received a single subcutaneous injection of Placebo to Canakinumab. Patients must have had documented diagnosis of Type 2 Diabetes Mellitus for 3 months prior to screening and be on a stable dose of Insulin, 2 insulin injections per day for a total daily dose of less than 100 U with or without Metformin (Met)for 3 months prior to screening	Canakinumab 150 mg in Participants With IGT Eligible participants received a single subcutaneous injection of Canakinumab 150 mg. Patients must have had Impaired Glucose Tolerance (IGT) as defined by the World Health Organization (WHO) criteria confirmed at screening visit.	Placebo in Participants With IGT Eligible participants received a single subcutaneous injection of Placebo to Canakinumab. Patients must have had Impaired Glucose Tolerance (IGT) as defined by the World Health Organization (WHO) criteria confirmed at screening visit.
Overall Study STARTED	33	17	33	17	32	16	28	15	28	27
Overall Study COMPLETED	33	16	33	16	32	14	28	15	28	23
Overall Study NOT COMPLETED	0	1	0	1	0	2	0	0	0	4

Reasons for withdrawal

Measure	Canakinumab 150 mg + Metformin Eligible participants received a single subcutaneous injection Canakinumab 150 mg. Patients must have had documented diagnosis of Type 2 Diabetes Mellitus and be on a stable dose of Metformin (Met) monotherapy treatment at least 1000 mg/day for 3 months prior to screening	Placebo + Metformin Eligible participants received a single subcutaneous injection of Placebo to Canakinumab. Patients must have had documented diagnosis of Type 2 Diabetes Mellitus and be on a stable dose of Metformin (Met) monotherapy treatment at least 1000 mg/day for 3 months prior to screening	Canakinumab 150 mg + Metformin + Sulfonylurea Eligible participants received a single subcutaneous injection of Canakinumab 150 mg.Patients must have had documented diagnosis of Type 2 Diabetes Mellitus and be on a stable dose of Metformin (Met) at least 1000 mg/day , and a Sulfonylurea (Sulfonyl), at least 1/2 the maximally labeled dose combination therapy, for 3 months prior to screening.	Placebo + Metformin + Sulfonylurea Eligible participants received a single subcutaneous injection of Placebo to Canakinumab.Patients must have had documented diagnosis of Type 2 Diabetes Mellitus and be on a stable dose of Metformin (Met) at least 1000 mg/day , and a Sulfonylurea (Sulfonyl), at least 1/2 the maximally labeled dose combination therapy, for 3 months prior to screening.	Canakinumab 150 mg Canakinumab 150 mg + Met + Sulfonyl + Thia Eligible participants received a single subcutaneous injection of Canakinumab 150 mg.Patients must have had documented diagnosis of Type 2 Diabetes Mellitus and be on a stable dose of Metformin (Met) at least 1000 mg/day , and a Sulfonylurea (Sulfonyl), at least 1/2 the maximally labeled dose, and a Thiazolidinedione (Thiaz)at least 1/2 the maximally labeled dose combination therapy, for 3 months prior to screening.	Placebo + Met + Sulfonyl + Thiaz Eligible participants received a single subcutaneous injection of Placebo to Canakinumab. Patients must have had documented diagnosis of Type 2 Diabetes Mellitus and be on a stable dose of Metformin (Met) at least 1000 mg/day , and a Sulfonylurea (Sulfonyl), at least 1/2 the maximally labeled dose, and a Thiazolidinedione (Thiaz)at least 1/2 the maximally labeled dose combination therapy, for 3 months prior to screening.	Canakinumab 150 mg + Insulin Eligible participants received a single subcutaneous injection of Canakinumab 150 mg. Patients must have had documented diagnosis of Type 2 Diabetes Mellitus for 3 months prior to screening and be on a stable dose of Insulin, 2 insulin injections per day for a total daily dose of less than 100 U with or without Metformin (Met)for 3 months prior to screening	Placebo + Insulin Eligible participants received a single subcutaneous injection of Placebo to Canakinumab. Patients must have had documented diagnosis of Type 2 Diabetes Mellitus for 3 months prior to screening and be on a stable dose of Insulin, 2 insulin injections per day for a total daily dose of less than 100 U with or without Metformin (Met)for 3 months prior to screening	Canakinumab 150 mg in Participants With IGT Eligible participants received a single subcutaneous injection of Canakinumab 150 mg. Patients must have had Impaired Glucose Tolerance (IGT) as defined by the World Health Organization (WHO) criteria confirmed at screening visit.	Placebo in Participants With IGT Eligible participants received a single subcutaneous injection of Placebo to Canakinumab. Patients must have had Impaired Glucose Tolerance (IGT) as defined by the World Health Organization (WHO) criteria confirmed at screening visit.
Overall Study Withdrawal by Subject	0	0	0	0	0	2	0	0	0	3
Overall Study Administrative problems; misrandomized	0	0	0	1	0	0	0	0	0	1
Overall Study Lost to Follow-up	0	1	0	0	0	0	0	0	0	0

Baseline Characteristics

To Compare the Effect of a Subcutaneous Canakinumab Administration to Placebo in Patients With Impaired Glucose Tolerance or Patients With Type 2 Diabetes With Differing Baseline Diabetes Therapies

Baseline characteristics by cohort

Measure	Canakinumab 150 mg + Metformin n=33 Participants Eligible participants received a single subcutaneous injection Canakinumab 150 mg. Patients must have had documented diagnosis of Type 2 Diabetes Mellitus and be on a stable dose of Metformin (Met) monotherapy treatment at least 1000 mg/day for 3 months prior to screening	Placebo + Metformin n=17 Participants Eligible participants received a single subcutaneous injection of Placebo to Canakinumab. Patients must have had documented diagnosis of Type 2 Diabetes Mellitus and be on a stable dose of Metformin (Met) monotherapy treatment at least 1000 mg/day for 3 months prior to screening	Canakinumab 150 mg + Metformin + Sulfonylurea n=33 Participants Eligible participants received a single subcutaneous injection of Canakinumab 150 mg.Patients must have had documented diagnosis of Type 2 Diabetes Mellitus and be on a stable dose of Metformin (Met) at least 1000 mg/day , and a Sulfonylurea (Sulfonyl), at least 1/2 the maximally labeled dose combination therapy, for 3 months prior to screening.	Placebo + Metformin + Sulfonylurea n=17 Participants Eligible participants received a single subcutaneous injection of Placebo to Canakinumab.Patients must have had documented diagnosis of Type 2 Diabetes Mellitus and be on a stable dose of Metformin (Met) at least 1000 mg/day , and a Sulfonylurea (Sulfonyl), at least 1/2 the maximally labeled dose combination therapy, for 3 months prior to screening.	Canakinumab 150 mg Canakinumab 150 mg + Met + Sulfonyl + Thia n=32 Participants Eligible participants received a single subcutaneous injection of Canakinumab 150 mg.Patients must have had documented diagnosis of Type 2 Diabetes Mellitus and be on a stable dose of Metformin (Met) at least 1000 mg/day , and a Sulfonylurea (Sulfonyl), at least 1/2 the maximally labeled dose, and a Thiazolidinedione (Thiaz)at least 1/2 the maximally labeled dose combination therapy, for 3 months prior to screening.	Placebo + Met + Sulfonyl + Thiaz n=16 Participants Eligible participants received a single subcutaneous injection of Placebo to Canakinumab. Patients must have had documented diagnosis of Type 2 Diabetes Mellitus and be on a stable dose of Metformin (Met) at least 1000 mg/day , and a Sulfonylurea (Sulfonyl), at least 1/2 the maximally labeled dose, and a Thiazolidinedione (Thiaz)at least 1/2 the maximally labeled dose combination therapy, for 3 months prior to screening.	Canakinumab 150 mg + Insulin n=28 Participants Eligible participants received a single subcutaneous injection of Canakinumab 150 mg. Patients must have had documented diagnosis of Type 2 Diabetes Mellitus for 3 months prior to screening and be on a stable dose of Insulin, 2 insulin injections per day for a total daily dose of less than 100 U with or without Metformin (Met)for 3 months prior to screening	Placebo + Insulin n=15 Participants Eligible participants received a single subcutaneous injection of Placebo to Canakinumab. Patients must have had documented diagnosis of Type 2 Diabetes Mellitus for 3 months prior to screening and be on a stable dose of Insulin, 2 insulin injections per day for a total daily dose of less than 100 U with or without Metformin (Met)for 3 months prior to screening	Canakinumab 150 mg in Participants With IGT n=28 Participants Eligible participants received a single subcutaneous injection of Canakinumab 150 mg. Patients must have had Impaired Glucose Tolerance (IGT) as defined by the World Health Organization (WHO) criteria confirmed at screening visit.	Placebo in Participants With IGT n=27 Participants Eligible participants received a single subcutaneous injection of Placebo to Canakinumab. Patients must have had Impaired Glucose Tolerance (IGT) as defined by the World Health Organization (WHO) criteria confirmed at screening visit.	Total n=246 Participants Total of all reporting groups
Age, Customized	55.9 years STANDARD_DEVIATION 10.50 • n=5 Participants	56.5 years STANDARD_DEVIATION 9.30 • n=7 Participants	60.0 years STANDARD_DEVIATION 8.17 • n=5 Participants	59.4 years STANDARD_DEVIATION 8.02 • n=4 Participants	59.1 years STANDARD_DEVIATION 10.63 • n=21 Participants	57.2 years STANDARD_DEVIATION 9.39 • n=10 Participants	58.6 years STANDARD_DEVIATION 10.11 • n=115 Participants	57.0 years STANDARD_DEVIATION 13.86 • n=24 Participants	52.8 years STANDARD_DEVIATION 10.90 • n=42 Participants	57.6 years STANDARD_DEVIATION 10.07 • n=42 Participants	57.4 years STANDARD_DEVIATION 10.16 • n=42 Participants
Sex: Female, Male Female	19 Participants n=5 Participants	3 Participants n=7 Participants	14 Participants n=5 Participants	10 Participants n=4 Participants	11 Participants n=21 Participants	5 Participants n=10 Participants	13 Participants n=115 Participants	10 Participants n=24 Participants	12 Participants n=42 Participants	16 Participants n=42 Participants	113 Participants n=42 Participants
Sex: Female, Male Male	14 Participants n=5 Participants	14 Participants n=7 Participants	19 Participants n=5 Participants	7 Participants n=4 Participants	21 Participants n=21 Participants	11 Participants n=10 Participants	15 Participants n=115 Participants	5 Participants n=24 Participants	16 Participants n=42 Participants	11 Participants n=42 Participants	133 Participants n=42 Participants

PRIMARY outcome

Timeframe: Baseline, 4 weeks

Population: Participants from the full analysis set who participated in the meal challenge and who had at least 1 post-baseline absolute glucose measurement at 2 hours.

Change in Insulin Secretion Rate stimulated by Liquid mixed-meal challenge. Blood samples were taken prior to and after meal for glucose and insulin at sample times: -20, -10, -1 and 10, 20, 30, 60, 90, 120, 180, and 240 minutes relative to the start of the meal.A mixed model with treatment fitted as fixed effect, and population and the interaction of population and treatment fitted as random effects were used for the comparison of Canakinumab versus placebo within each T2DM population. The mixed model did not include patients from the IGT population

Outcome measures

Measure	Canakinumab 150 mg + Metformin n=32 Participants Eligible participants received a single subcutaneous injection Canakinumab 150 mg. Patients must have had documented diagnosis of Type 2 Diabetes Mellitus and be on a stable dose of Metformin (Met) monotherapy treatment at least 1000 mg/day for 3 months prior to screening	Placebo + Metformin n=16 Participants Eligible participants received a single subcutaneous injection of Placebo to Canakinumab. Patients must have had documented diagnosis of Type 2 Diabetes Mellitus and be on a stable dose of Metformin (Met) monotherapy treatment at least 1000 mg/day for 3 months prior to screening	Canakinumab 150 mg + Metformin + Sulfonylurea n=31 Participants Eligible participants received a single subcutaneous injection of Canakinumab 150 mg.Patients must have had documented diagnosis of Type 2 Diabetes Mellitus and be on a stable dose of Metformin (Met) at least 1000 mg/day , and a Sulfonylurea (Sulfonyl), at least 1/2 the maximally labeled dose combination therapy, for 3 months prior to screening.	Placebo + Metformin + Sulfonylurea n=15 Participants Eligible participants received a single subcutaneous injection of Placebo to Canakinumab.Patients must have had documented diagnosis of Type 2 Diabetes Mellitus and be on a stable dose of Metformin (Met) at least 1000 mg/day , and a Sulfonylurea (Sulfonyl), at least 1/2 the maximally labeled dose combination therapy, for 3 months prior to screening.	Canakinumab 150 mg Canakinumab 150 mg + Met + Sulfonyl + Thia n=31 Participants Eligible participants received a single subcutaneous injection of Canakinumab 150 mg.Patients must have had documented diagnosis of Type 2 Diabetes Mellitus and be on a stable dose of Metformin (Met) at least 1000 mg/day , and a Sulfonylurea (Sulfonyl), at least 1/2 the maximally labeled dose, and a Thiazolidinedione (Thiaz)at least 1/2 the maximally labeled dose combination therapy, for 3 months prior to screening.	Placebo + Met + Sulfonyl + Thiaz n=14 Participants Eligible participants received a single subcutaneous injection of Placebo to Canakinumab. Patients must have had documented diagnosis of Type 2 Diabetes Mellitus and be on a stable dose of Metformin (Met) at least 1000 mg/day , and a Sulfonylurea (Sulfonyl), at least 1/2 the maximally labeled dose, and a Thiazolidinedione (Thiaz)at least 1/2 the maximally labeled dose combination therapy, for 3 months prior to screening.	Canakinumab 150 mg + Insulin n=26 Participants Eligible participants received a single subcutaneous injection of Canakinumab 150 mg. Patients must have had documented diagnosis of Type 2 Diabetes Mellitus for 3 months prior to screening and be on a stable dose of Insulin, 2 insulin injections per day for a total daily dose of less than 100 U with or without Metformin (Met)for 3 months prior to screening	Placebo + Insulin n=15 Participants Eligible participants received a single subcutaneous injection of Placebo to Canakinumab. Patients must have had documented diagnosis of Type 2 Diabetes Mellitus for 3 months prior to screening and be on a stable dose of Insulin, 2 insulin injections per day for a total daily dose of less than 100 U with or without Metformin (Met)for 3 months prior to screening	Canakinumab 150 mg in Participants With IGT n=28 Participants Eligible participants received a single subcutaneous injection of Canakinumab 150 mg. Patients must have had Impaired Glucose Tolerance (IGT) as defined by the World Health Organization (WHO) criteria confirmed at screening visit.	Placebo in Participants With IGT n=21 Participants Eligible participants received a single subcutaneous injection of Placebo to Canakinumab. Patients must have had Impaired Glucose Tolerance (IGT) as defined by the World Health Organization (WHO) criteria confirmed at screening visit.
Mean Change in Meal Stimulated Insulin Secretion Rate (ISR) Relative to Glucose 0-2 Hours, From Baseline to 4 Weeks.	-0.06 pmol/min/m^2/mmol/L Standard Error 0.943	-0.23 pmol/min/m^2/mmol/L Standard Error 1.334	0.04 pmol/min/m^2/mmol/L Standard Error 0.958	0.45 pmol/min/m^2/mmol/L Standard Error 1.378	-0.79 pmol/min/m^2/mmol/L Standard Error 0.958	1.16 pmol/min/m^2/mmol/L Standard Error 1.426	1.23 pmol/min/m^2/mmol/L Standard Error 1.046	-0.49 pmol/min/m^2/mmol/L Standard Error 1.378	-1.50 pmol/min/m^2/mmol/L Standard Error 1.975	-1.93 pmol/min/m^2/mmol/L Standard Error 1.737

SECONDARY outcome

Timeframe: Baseline, 4 weeks

Population: Participants from the full analysis set who participated in the meal challenge and who had at least 1 post-baseline absolute glucose measurement at 2 hours.

Change in Insulin Secretion Rate stimulated by Liquid mixed-meal challenge Blood samples were taken prior to and after meal for glucose and insulin at sample times: -20, -10, -1 and 10, 20, 30, 60, 90, 120, 180, and 240 minutes relative to the start of the meal. A mixed model with treatment fitted as fixed effect, and population and the interaction of population and treatment fitted as random effects were used for the comparison of Canakinumab versus placebo within each T2DM population. The mixed model did not include participants from the IGT population

Outcome measures

Measure	Canakinumab 150 mg + Metformin n=32 Participants Eligible participants received a single subcutaneous injection Canakinumab 150 mg. Patients must have had documented diagnosis of Type 2 Diabetes Mellitus and be on a stable dose of Metformin (Met) monotherapy treatment at least 1000 mg/day for 3 months prior to screening	Placebo + Metformin n=16 Participants Eligible participants received a single subcutaneous injection of Placebo to Canakinumab. Patients must have had documented diagnosis of Type 2 Diabetes Mellitus and be on a stable dose of Metformin (Met) monotherapy treatment at least 1000 mg/day for 3 months prior to screening	Canakinumab 150 mg + Metformin + Sulfonylurea n=30 Participants Eligible participants received a single subcutaneous injection of Canakinumab 150 mg.Patients must have had documented diagnosis of Type 2 Diabetes Mellitus and be on a stable dose of Metformin (Met) at least 1000 mg/day , and a Sulfonylurea (Sulfonyl), at least 1/2 the maximally labeled dose combination therapy, for 3 months prior to screening.	Placebo + Metformin + Sulfonylurea n=15 Participants Eligible participants received a single subcutaneous injection of Placebo to Canakinumab.Patients must have had documented diagnosis of Type 2 Diabetes Mellitus and be on a stable dose of Metformin (Met) at least 1000 mg/day , and a Sulfonylurea (Sulfonyl), at least 1/2 the maximally labeled dose combination therapy, for 3 months prior to screening.	Canakinumab 150 mg Canakinumab 150 mg + Met + Sulfonyl + Thia n=31 Participants Eligible participants received a single subcutaneous injection of Canakinumab 150 mg.Patients must have had documented diagnosis of Type 2 Diabetes Mellitus and be on a stable dose of Metformin (Met) at least 1000 mg/day , and a Sulfonylurea (Sulfonyl), at least 1/2 the maximally labeled dose, and a Thiazolidinedione (Thiaz)at least 1/2 the maximally labeled dose combination therapy, for 3 months prior to screening.	Placebo + Met + Sulfonyl + Thiaz n=14 Participants Eligible participants received a single subcutaneous injection of Placebo to Canakinumab. Patients must have had documented diagnosis of Type 2 Diabetes Mellitus and be on a stable dose of Metformin (Met) at least 1000 mg/day , and a Sulfonylurea (Sulfonyl), at least 1/2 the maximally labeled dose, and a Thiazolidinedione (Thiaz)at least 1/2 the maximally labeled dose combination therapy, for 3 months prior to screening.	Canakinumab 150 mg + Insulin n=26 Participants Eligible participants received a single subcutaneous injection of Canakinumab 150 mg. Patients must have had documented diagnosis of Type 2 Diabetes Mellitus for 3 months prior to screening and be on a stable dose of Insulin, 2 insulin injections per day for a total daily dose of less than 100 U with or without Metformin (Met)for 3 months prior to screening	Placebo + Insulin n=15 Participants Eligible participants received a single subcutaneous injection of Placebo to Canakinumab. Patients must have had documented diagnosis of Type 2 Diabetes Mellitus for 3 months prior to screening and be on a stable dose of Insulin, 2 insulin injections per day for a total daily dose of less than 100 U with or without Metformin (Met)for 3 months prior to screening	Canakinumab 150 mg in Participants With IGT n=28 Participants Eligible participants received a single subcutaneous injection of Canakinumab 150 mg. Patients must have had Impaired Glucose Tolerance (IGT) as defined by the World Health Organization (WHO) criteria confirmed at screening visit.	Placebo in Participants With IGT n=20 Participants Eligible participants received a single subcutaneous injection of Placebo to Canakinumab. Patients must have had Impaired Glucose Tolerance (IGT) as defined by the World Health Organization (WHO) criteria confirmed at screening visit.
Mean Change in Meal Stimulated Insulin Secretion Rate (ISR) Relative to Glucose 2-4 Hours, From Baseline to 4 Weeks	0.21 pmol/min/m^2/mmol/L Standard Error 2.000	-2.15 pmol/min/m^2/mmol/L Standard Error 2.829	-2.98 pmol/min/m^2/mmol/L Standard Error 2.066	2.02 pmol/min/m^2/mmol/L Standard Error 2.921	0.15 pmol/min/m^2/mmol/L Standard Error 2.032	1.19 pmol/min/m^2/mmol/L Standard Error 3.024	-0.43 pmol/min/m^2/mmol/L Standard Error 2.219	-0.51 pmol/min/m^2/mmol/L Standard Error 2.921	-0.71 pmol/min/m^2/mmol/L Standard Error 1.040	-1.00 pmol/min/m^2/mmol/L Standard Error 1.518

SECONDARY outcome

Timeframe: Baseline, 4 weeks

Population: Participants from the full analysis set who participated in the meal challenge and who had at least 1 post-baseline absolute glucose measurement at 2 hours.

Change in Insulin Secretion Rate stimulated by Liquid mixed-meal challenge. Blood samples were taken prior to and after meal for glucose, insulin and C-peptide at sample times: -20, -10, -1 and 10, 20, 30, 60, 90, 120, 180, and 240 minutes relative to the start of the meal. A mixed model with treatment fitted as fixed effect, and population and the interaction of population and treatment fitted as random effects were used for the comparison of Canakinumab versus placebo within each T2DM population. The mixed model did not include participants from the IGT population.

Outcome measures

Measure	Canakinumab 150 mg + Metformin n=33 Participants Eligible participants received a single subcutaneous injection Canakinumab 150 mg. Patients must have had documented diagnosis of Type 2 Diabetes Mellitus and be on a stable dose of Metformin (Met) monotherapy treatment at least 1000 mg/day for 3 months prior to screening	Placebo + Metformin n=16 Participants Eligible participants received a single subcutaneous injection of Placebo to Canakinumab. Patients must have had documented diagnosis of Type 2 Diabetes Mellitus and be on a stable dose of Metformin (Met) monotherapy treatment at least 1000 mg/day for 3 months prior to screening	Canakinumab 150 mg + Metformin + Sulfonylurea n=31 Participants Eligible participants received a single subcutaneous injection of Canakinumab 150 mg.Patients must have had documented diagnosis of Type 2 Diabetes Mellitus and be on a stable dose of Metformin (Met) at least 1000 mg/day , and a Sulfonylurea (Sulfonyl), at least 1/2 the maximally labeled dose combination therapy, for 3 months prior to screening.	Placebo + Metformin + Sulfonylurea n=15 Participants Eligible participants received a single subcutaneous injection of Placebo to Canakinumab.Patients must have had documented diagnosis of Type 2 Diabetes Mellitus and be on a stable dose of Metformin (Met) at least 1000 mg/day , and a Sulfonylurea (Sulfonyl), at least 1/2 the maximally labeled dose combination therapy, for 3 months prior to screening.	Canakinumab 150 mg Canakinumab 150 mg + Met + Sulfonyl + Thia n=32 Participants Eligible participants received a single subcutaneous injection of Canakinumab 150 mg.Patients must have had documented diagnosis of Type 2 Diabetes Mellitus and be on a stable dose of Metformin (Met) at least 1000 mg/day , and a Sulfonylurea (Sulfonyl), at least 1/2 the maximally labeled dose, and a Thiazolidinedione (Thiaz)at least 1/2 the maximally labeled dose combination therapy, for 3 months prior to screening.	Placebo + Met + Sulfonyl + Thiaz n=14 Participants Eligible participants received a single subcutaneous injection of Placebo to Canakinumab. Patients must have had documented diagnosis of Type 2 Diabetes Mellitus and be on a stable dose of Metformin (Met) at least 1000 mg/day , and a Sulfonylurea (Sulfonyl), at least 1/2 the maximally labeled dose, and a Thiazolidinedione (Thiaz)at least 1/2 the maximally labeled dose combination therapy, for 3 months prior to screening.	Canakinumab 150 mg + Insulin n=26 Participants Eligible participants received a single subcutaneous injection of Canakinumab 150 mg. Patients must have had documented diagnosis of Type 2 Diabetes Mellitus for 3 months prior to screening and be on a stable dose of Insulin, 2 insulin injections per day for a total daily dose of less than 100 U with or without Metformin (Met)for 3 months prior to screening	Placebo + Insulin n=15 Participants Eligible participants received a single subcutaneous injection of Placebo to Canakinumab. Patients must have had documented diagnosis of Type 2 Diabetes Mellitus for 3 months prior to screening and be on a stable dose of Insulin, 2 insulin injections per day for a total daily dose of less than 100 U with or without Metformin (Met)for 3 months prior to screening	Canakinumab 150 mg in Participants With IGT n=28 Participants Eligible participants received a single subcutaneous injection of Canakinumab 150 mg. Patients must have had Impaired Glucose Tolerance (IGT) as defined by the World Health Organization (WHO) criteria confirmed at screening visit.	Placebo in Participants With IGT n=21 Participants Eligible participants received a single subcutaneous injection of Placebo to Canakinumab. Patients must have had Impaired Glucose Tolerance (IGT) as defined by the World Health Organization (WHO) criteria confirmed at screening visit.
Mean Change in Meal Stimulated Insulin Secretion Rate (ISR) Relative to Glucose 0-4 Hours, From Baseline to 4 Weeks.	0.44 pmol/min/m^2/mmol/L Standard Error 0.858	-0.99 pmol/min/m^2/mmol/L Standard Error 1.232	-0.32 pmol/min/m^2/mmol/L Standard Error 0.885	1.22 pmol/min/m^2/mmol/L Standard Error 1.272	-0.63 pmol/min/m^2/mmol/L Standard Error 0.871	1.24 pmol/min/m^2/mmol/L Standard Error 1.317	0.53 pmol/min/m^2/mmol/L Standard Error 0.966	-0.49 pmol/min/m^2/mmol/L Standard Error 1.272	-1.38 pmol/min/m^2/mmol/L Standard Error 1.356	-1.35 pmol/min/m^2/mmol/L Standard Error 1.330

SECONDARY outcome

Timeframe: Baseline, 4 weeks

Population: Participants from the full analysis set who participated in the meal challenge and who had at least 1 post-baseline absolute glucose measurement at 2 hours.

Change in Fasting Glucose Level measured from plasma taken at Baseline and after 4 weeks of treatment.

A mixed model with treatment fitted as fixed effect, and population and the interaction of population and treatment fitted as random effects were used for the comparison of Canakinumab versus placebo within each T2DM population. The mixed model did not include participants from the IGT population

Outcome measures

Measure	Canakinumab 150 mg + Metformin n=33 Participants Eligible participants received a single subcutaneous injection Canakinumab 150 mg. Patients must have had documented diagnosis of Type 2 Diabetes Mellitus and be on a stable dose of Metformin (Met) monotherapy treatment at least 1000 mg/day for 3 months prior to screening	Placebo + Metformin n=16 Participants Eligible participants received a single subcutaneous injection of Placebo to Canakinumab. Patients must have had documented diagnosis of Type 2 Diabetes Mellitus and be on a stable dose of Metformin (Met) monotherapy treatment at least 1000 mg/day for 3 months prior to screening	Canakinumab 150 mg + Metformin + Sulfonylurea n=31 Participants Eligible participants received a single subcutaneous injection of Canakinumab 150 mg.Patients must have had documented diagnosis of Type 2 Diabetes Mellitus and be on a stable dose of Metformin (Met) at least 1000 mg/day , and a Sulfonylurea (Sulfonyl), at least 1/2 the maximally labeled dose combination therapy, for 3 months prior to screening.	Placebo + Metformin + Sulfonylurea n=16 Participants Eligible participants received a single subcutaneous injection of Placebo to Canakinumab.Patients must have had documented diagnosis of Type 2 Diabetes Mellitus and be on a stable dose of Metformin (Met) at least 1000 mg/day , and a Sulfonylurea (Sulfonyl), at least 1/2 the maximally labeled dose combination therapy, for 3 months prior to screening.	Canakinumab 150 mg Canakinumab 150 mg + Met + Sulfonyl + Thia n=32 Participants Eligible participants received a single subcutaneous injection of Canakinumab 150 mg.Patients must have had documented diagnosis of Type 2 Diabetes Mellitus and be on a stable dose of Metformin (Met) at least 1000 mg/day , and a Sulfonylurea (Sulfonyl), at least 1/2 the maximally labeled dose, and a Thiazolidinedione (Thiaz)at least 1/2 the maximally labeled dose combination therapy, for 3 months prior to screening.	Placebo + Met + Sulfonyl + Thiaz n=14 Participants Eligible participants received a single subcutaneous injection of Placebo to Canakinumab. Patients must have had documented diagnosis of Type 2 Diabetes Mellitus and be on a stable dose of Metformin (Met) at least 1000 mg/day , and a Sulfonylurea (Sulfonyl), at least 1/2 the maximally labeled dose, and a Thiazolidinedione (Thiaz)at least 1/2 the maximally labeled dose combination therapy, for 3 months prior to screening.	Canakinumab 150 mg + Insulin n=26 Participants Eligible participants received a single subcutaneous injection of Canakinumab 150 mg. Patients must have had documented diagnosis of Type 2 Diabetes Mellitus for 3 months prior to screening and be on a stable dose of Insulin, 2 insulin injections per day for a total daily dose of less than 100 U with or without Metformin (Met)for 3 months prior to screening	Placebo + Insulin n=15 Participants Eligible participants received a single subcutaneous injection of Placebo to Canakinumab. Patients must have had documented diagnosis of Type 2 Diabetes Mellitus for 3 months prior to screening and be on a stable dose of Insulin, 2 insulin injections per day for a total daily dose of less than 100 U with or without Metformin (Met)for 3 months prior to screening	Canakinumab 150 mg in Participants With IGT n=28 Participants Eligible participants received a single subcutaneous injection of Canakinumab 150 mg. Patients must have had Impaired Glucose Tolerance (IGT) as defined by the World Health Organization (WHO) criteria confirmed at screening visit.	Placebo in Participants With IGT n=21 Participants Eligible participants received a single subcutaneous injection of Placebo to Canakinumab. Patients must have had Impaired Glucose Tolerance (IGT) as defined by the World Health Organization (WHO) criteria confirmed at screening visit.
Mean Change in Fasting Plasma Glucose, From Baseline to 4 Weeks	-0.32 mmol/L Standard Error 0.272	0.33 mmol/L Standard Error 0.391	-0.20 mmol/L Standard Error 0.281	-0.23 mmol/L Standard Error 0.391	-0.33 mmol/L Standard Error 0.276	-0.36 mmol/L Standard Error 0.418	-0.26 mmol/L Standard Error 0.307	-0.80 mmol/L Standard Error 0.404	-0.06 mmol/L Standard Error 0.107	0.10 mmol/L Standard Error 0.094

SECONDARY outcome

Timeframe: Baseline, 4 weeks

Population: Participants from the full analysis set who participated in the meal challenge and who had at least 1 post-baseline absolute glucose measurement at 2 hours.

Change in Fructosamine Level taken from plasma, measured at Baseline and after 4 weeks of treatment.

A mixed model with treatment fitted as fixed effect, and population and the interaction of population and treatment fitted as random effects were used for the comparison of Canakinumab versus placebo within each T2DM population. The mixed model did not include participants from the IGT population

Outcome measures

Measure	Canakinumab 150 mg + Metformin n=33 Participants Eligible participants received a single subcutaneous injection Canakinumab 150 mg. Patients must have had documented diagnosis of Type 2 Diabetes Mellitus and be on a stable dose of Metformin (Met) monotherapy treatment at least 1000 mg/day for 3 months prior to screening	Placebo + Metformin n=16 Participants Eligible participants received a single subcutaneous injection of Placebo to Canakinumab. Patients must have had documented diagnosis of Type 2 Diabetes Mellitus and be on a stable dose of Metformin (Met) monotherapy treatment at least 1000 mg/day for 3 months prior to screening	Canakinumab 150 mg + Metformin + Sulfonylurea n=31 Participants Eligible participants received a single subcutaneous injection of Canakinumab 150 mg.Patients must have had documented diagnosis of Type 2 Diabetes Mellitus and be on a stable dose of Metformin (Met) at least 1000 mg/day , and a Sulfonylurea (Sulfonyl), at least 1/2 the maximally labeled dose combination therapy, for 3 months prior to screening.	Placebo + Metformin + Sulfonylurea n=16 Participants Eligible participants received a single subcutaneous injection of Placebo to Canakinumab.Patients must have had documented diagnosis of Type 2 Diabetes Mellitus and be on a stable dose of Metformin (Met) at least 1000 mg/day , and a Sulfonylurea (Sulfonyl), at least 1/2 the maximally labeled dose combination therapy, for 3 months prior to screening.	Canakinumab 150 mg Canakinumab 150 mg + Met + Sulfonyl + Thia n=32 Participants Eligible participants received a single subcutaneous injection of Canakinumab 150 mg.Patients must have had documented diagnosis of Type 2 Diabetes Mellitus and be on a stable dose of Metformin (Met) at least 1000 mg/day , and a Sulfonylurea (Sulfonyl), at least 1/2 the maximally labeled dose, and a Thiazolidinedione (Thiaz)at least 1/2 the maximally labeled dose combination therapy, for 3 months prior to screening.	Placebo + Met + Sulfonyl + Thiaz n=14 Participants Eligible participants received a single subcutaneous injection of Placebo to Canakinumab. Patients must have had documented diagnosis of Type 2 Diabetes Mellitus and be on a stable dose of Metformin (Met) at least 1000 mg/day , and a Sulfonylurea (Sulfonyl), at least 1/2 the maximally labeled dose, and a Thiazolidinedione (Thiaz)at least 1/2 the maximally labeled dose combination therapy, for 3 months prior to screening.	Canakinumab 150 mg + Insulin n=27 Participants Eligible participants received a single subcutaneous injection of Canakinumab 150 mg. Patients must have had documented diagnosis of Type 2 Diabetes Mellitus for 3 months prior to screening and be on a stable dose of Insulin, 2 insulin injections per day for a total daily dose of less than 100 U with or without Metformin (Met)for 3 months prior to screening	Placebo + Insulin n=15 Participants Eligible participants received a single subcutaneous injection of Placebo to Canakinumab. Patients must have had documented diagnosis of Type 2 Diabetes Mellitus for 3 months prior to screening and be on a stable dose of Insulin, 2 insulin injections per day for a total daily dose of less than 100 U with or without Metformin (Met)for 3 months prior to screening	Canakinumab 150 mg in Participants With IGT n=28 Participants Eligible participants received a single subcutaneous injection of Canakinumab 150 mg. Patients must have had Impaired Glucose Tolerance (IGT) as defined by the World Health Organization (WHO) criteria confirmed at screening visit.	Placebo in Participants With IGT n=23 Participants Eligible participants received a single subcutaneous injection of Placebo to Canakinumab. Patients must have had Impaired Glucose Tolerance (IGT) as defined by the World Health Organization (WHO) criteria confirmed at screening visit.
Mean Change in Fructosamine, From Baseline to 4 Weeks	-5.30 mmol/L Standard Error 3.727	-0.75 mmol/L Standard Error 5.353	-3.45 mmol/L Standard Error 3.846	-7.50 mmol/L Standard Error 5.353	-1.81 mmol/L Standard Error 3.785	-3.07 mmol/L Standard Error 5.722	-3.00 mmol/L Standard Error 4.121	-19.73 mmol/L Standard Error 5.528	-6.36 mmol/L Standard Error 3.259	1.39 mmol/L Standard Error 3813

SECONDARY outcome

Timeframe: Baseline, 4 weeks

Population: Participants from the full analysis set who participated in the meal challenge and who had at least 1 post-baseline absolute glucose measurement at 2 hours.

Change in Fasting Insulin level taken from plasma, measured at Baseline and after 4 weeks of treatment.

A mixed model with treatment fitted as fixed effect, and population and the interaction of population and treatment fitted as random effects were used for the comparison of Canakinumab versus placebo within each T2DM population. The mixed model did not include participants from the IGT population

Outcome measures

Measure	Canakinumab 150 mg + Metformin n=33 Participants Eligible participants received a single subcutaneous injection Canakinumab 150 mg. Patients must have had documented diagnosis of Type 2 Diabetes Mellitus and be on a stable dose of Metformin (Met) monotherapy treatment at least 1000 mg/day for 3 months prior to screening	Placebo + Metformin n=15 Participants Eligible participants received a single subcutaneous injection of Placebo to Canakinumab. Patients must have had documented diagnosis of Type 2 Diabetes Mellitus and be on a stable dose of Metformin (Met) monotherapy treatment at least 1000 mg/day for 3 months prior to screening	Canakinumab 150 mg + Metformin + Sulfonylurea n=30 Participants Eligible participants received a single subcutaneous injection of Canakinumab 150 mg.Patients must have had documented diagnosis of Type 2 Diabetes Mellitus and be on a stable dose of Metformin (Met) at least 1000 mg/day , and a Sulfonylurea (Sulfonyl), at least 1/2 the maximally labeled dose combination therapy, for 3 months prior to screening.	Placebo + Metformin + Sulfonylurea n=15 Participants Eligible participants received a single subcutaneous injection of Placebo to Canakinumab.Patients must have had documented diagnosis of Type 2 Diabetes Mellitus and be on a stable dose of Metformin (Met) at least 1000 mg/day , and a Sulfonylurea (Sulfonyl), at least 1/2 the maximally labeled dose combination therapy, for 3 months prior to screening.	Canakinumab 150 mg Canakinumab 150 mg + Met + Sulfonyl + Thia n=31 Participants Eligible participants received a single subcutaneous injection of Canakinumab 150 mg.Patients must have had documented diagnosis of Type 2 Diabetes Mellitus and be on a stable dose of Metformin (Met) at least 1000 mg/day , and a Sulfonylurea (Sulfonyl), at least 1/2 the maximally labeled dose, and a Thiazolidinedione (Thiaz)at least 1/2 the maximally labeled dose combination therapy, for 3 months prior to screening.	Placebo + Met + Sulfonyl + Thiaz n=13 Participants Eligible participants received a single subcutaneous injection of Placebo to Canakinumab. Patients must have had documented diagnosis of Type 2 Diabetes Mellitus and be on a stable dose of Metformin (Met) at least 1000 mg/day , and a Sulfonylurea (Sulfonyl), at least 1/2 the maximally labeled dose, and a Thiazolidinedione (Thiaz)at least 1/2 the maximally labeled dose combination therapy, for 3 months prior to screening.	Canakinumab 150 mg + Insulin n=26 Participants Eligible participants received a single subcutaneous injection of Canakinumab 150 mg. Patients must have had documented diagnosis of Type 2 Diabetes Mellitus for 3 months prior to screening and be on a stable dose of Insulin, 2 insulin injections per day for a total daily dose of less than 100 U with or without Metformin (Met)for 3 months prior to screening	Placebo + Insulin n=15 Participants Eligible participants received a single subcutaneous injection of Placebo to Canakinumab. Patients must have had documented diagnosis of Type 2 Diabetes Mellitus for 3 months prior to screening and be on a stable dose of Insulin, 2 insulin injections per day for a total daily dose of less than 100 U with or without Metformin (Met)for 3 months prior to screening	Canakinumab 150 mg in Participants With IGT n=28 Participants Eligible participants received a single subcutaneous injection of Canakinumab 150 mg. Patients must have had Impaired Glucose Tolerance (IGT) as defined by the World Health Organization (WHO) criteria confirmed at screening visit.	Placebo in Participants With IGT n=23 Participants Eligible participants received a single subcutaneous injection of Placebo to Canakinumab. Patients must have had Impaired Glucose Tolerance (IGT) as defined by the World Health Organization (WHO) criteria confirmed at screening visit.
Mean Change in Fasting Plasma Insulin, From Baseline to 4 Weeks	-3.58 pmol/L Standard Error 8.703	10.73 pmol/L Standard Error 12.908	-16.07 pmol/L Standard Error 9.128	-9.40 pmol/L Standard Error 12.908	-0.77 pmol/L Standard Error 8.979	2.31 pmol/L Standard Error 13.866	21.27 pmol/L Standard Error 9.805	25.67 pmol/L Standard Error 12.908	-.021 pmol/L Standard Error 6.093	-3.43 pmol/L Standard Error 4.554

SECONDARY outcome

Timeframe: Baseline, 4 weeks

Population: Participants from the full analysis set who participated in the meal challenge and who had at least 1 post-baseline absolute glucose measurement at 2 hours.

The Quantitative Insulin Sensitivity Check Index (QUICKI) score, measures insulin sensitivity which is the inverse of insulin resistance. The score is calculated by the equation: 1 /(log(fasting insulin µU/mL) + log(fasting glucose mg/dL)). In normal subjects the mean score ± SE is 0.366 ± 0.029.

A mixed model with treatment fitted as fixed effect, and population and the interaction of population and treatment fitted as random effects were used for the comparison of Canakinumab versus placebo within each T2DM population. The mixed model did not include participants from the IGT population.

Outcome measures

Measure	Canakinumab 150 mg + Metformin n=33 Participants Eligible participants received a single subcutaneous injection Canakinumab 150 mg. Patients must have had documented diagnosis of Type 2 Diabetes Mellitus and be on a stable dose of Metformin (Met) monotherapy treatment at least 1000 mg/day for 3 months prior to screening	Placebo + Metformin n=15 Participants Eligible participants received a single subcutaneous injection of Placebo to Canakinumab. Patients must have had documented diagnosis of Type 2 Diabetes Mellitus and be on a stable dose of Metformin (Met) monotherapy treatment at least 1000 mg/day for 3 months prior to screening	Canakinumab 150 mg + Metformin + Sulfonylurea n=30 Participants Eligible participants received a single subcutaneous injection of Canakinumab 150 mg.Patients must have had documented diagnosis of Type 2 Diabetes Mellitus and be on a stable dose of Metformin (Met) at least 1000 mg/day , and a Sulfonylurea (Sulfonyl), at least 1/2 the maximally labeled dose combination therapy, for 3 months prior to screening.	Placebo + Metformin + Sulfonylurea n=15 Participants Eligible participants received a single subcutaneous injection of Placebo to Canakinumab.Patients must have had documented diagnosis of Type 2 Diabetes Mellitus and be on a stable dose of Metformin (Met) at least 1000 mg/day , and a Sulfonylurea (Sulfonyl), at least 1/2 the maximally labeled dose combination therapy, for 3 months prior to screening.	Canakinumab 150 mg Canakinumab 150 mg + Met + Sulfonyl + Thia n=31 Participants Eligible participants received a single subcutaneous injection of Canakinumab 150 mg.Patients must have had documented diagnosis of Type 2 Diabetes Mellitus and be on a stable dose of Metformin (Met) at least 1000 mg/day , and a Sulfonylurea (Sulfonyl), at least 1/2 the maximally labeled dose, and a Thiazolidinedione (Thiaz)at least 1/2 the maximally labeled dose combination therapy, for 3 months prior to screening.	Placebo + Met + Sulfonyl + Thiaz n=13 Participants Eligible participants received a single subcutaneous injection of Placebo to Canakinumab. Patients must have had documented diagnosis of Type 2 Diabetes Mellitus and be on a stable dose of Metformin (Met) at least 1000 mg/day , and a Sulfonylurea (Sulfonyl), at least 1/2 the maximally labeled dose, and a Thiazolidinedione (Thiaz)at least 1/2 the maximally labeled dose combination therapy, for 3 months prior to screening.	Canakinumab 150 mg + Insulin n=25 Participants Eligible participants received a single subcutaneous injection of Canakinumab 150 mg. Patients must have had documented diagnosis of Type 2 Diabetes Mellitus for 3 months prior to screening and be on a stable dose of Insulin, 2 insulin injections per day for a total daily dose of less than 100 U with or without Metformin (Met)for 3 months prior to screening	Placebo + Insulin n=15 Participants Eligible participants received a single subcutaneous injection of Placebo to Canakinumab. Patients must have had documented diagnosis of Type 2 Diabetes Mellitus for 3 months prior to screening and be on a stable dose of Insulin, 2 insulin injections per day for a total daily dose of less than 100 U with or without Metformin (Met)for 3 months prior to screening	Canakinumab 150 mg in Participants With IGT n=28 Participants Eligible participants received a single subcutaneous injection of Canakinumab 150 mg. Patients must have had Impaired Glucose Tolerance (IGT) as defined by the World Health Organization (WHO) criteria confirmed at screening visit.	Placebo in Participants With IGT n=21 Participants Eligible participants received a single subcutaneous injection of Placebo to Canakinumab. Patients must have had Impaired Glucose Tolerance (IGT) as defined by the World Health Organization (WHO) criteria confirmed at screening visit.
Mean Change in Quantitative Insulin Sensitivity Check Index (QUICKI) Score, From Baseline to 4 Weeks	0.004 number Standard Error 0.0080	-0.000 number Standard Error 0.0119	0.002 number Standard Error 0.0084	0.009 number Standard Error 0.0119	0.018 number Standard Error 0.0083	-0.001 number Standard Error 0.0128	-0.003 number Standard Error 0.0092	0.005 number Standard Error 0.0119	-0.001 number Standard Error 0.0051	0.001 number Standard Error 0.0034

SECONDARY outcome

Timeframe: Baseline, 4 weeks

Population: Participants from the full analysis set who participated in the meal challenge and who had at least 1 post-baseline absolute glucose measurement at 2 hours.

GDI 1 is the product of insulin sensitivity index (Si)during the 1st phase of insulin secretion and β-cell function as measured by the acute insulin response (AIR).GDI 2 is the product of (Si)during the 2nd phase of insulin secretion and β-cell function as measured by the acute insulin response (AIR). A mixed model with treatment fitted as fixed effect, and population and the interaction of population and treatment fitted as random effects were used for the comparison of Canakinumab versus placebo within each T2DM population. The mixed model did not include participants from the IGT group.

Outcome measures

Measure	Canakinumab 150 mg + Metformin n=32 Participants Eligible participants received a single subcutaneous injection Canakinumab 150 mg. Patients must have had documented diagnosis of Type 2 Diabetes Mellitus and be on a stable dose of Metformin (Met) monotherapy treatment at least 1000 mg/day for 3 months prior to screening	Placebo + Metformin n=15 Participants Eligible participants received a single subcutaneous injection of Placebo to Canakinumab. Patients must have had documented diagnosis of Type 2 Diabetes Mellitus and be on a stable dose of Metformin (Met) monotherapy treatment at least 1000 mg/day for 3 months prior to screening	Canakinumab 150 mg + Metformin + Sulfonylurea n=30 Participants Eligible participants received a single subcutaneous injection of Canakinumab 150 mg.Patients must have had documented diagnosis of Type 2 Diabetes Mellitus and be on a stable dose of Metformin (Met) at least 1000 mg/day , and a Sulfonylurea (Sulfonyl), at least 1/2 the maximally labeled dose combination therapy, for 3 months prior to screening.	Placebo + Metformin + Sulfonylurea n=15 Participants Eligible participants received a single subcutaneous injection of Placebo to Canakinumab.Patients must have had documented diagnosis of Type 2 Diabetes Mellitus and be on a stable dose of Metformin (Met) at least 1000 mg/day , and a Sulfonylurea (Sulfonyl), at least 1/2 the maximally labeled dose combination therapy, for 3 months prior to screening.	Canakinumab 150 mg Canakinumab 150 mg + Met + Sulfonyl + Thia n=30 Participants Eligible participants received a single subcutaneous injection of Canakinumab 150 mg.Patients must have had documented diagnosis of Type 2 Diabetes Mellitus and be on a stable dose of Metformin (Met) at least 1000 mg/day , and a Sulfonylurea (Sulfonyl), at least 1/2 the maximally labeled dose, and a Thiazolidinedione (Thiaz)at least 1/2 the maximally labeled dose combination therapy, for 3 months prior to screening.	Placebo + Met + Sulfonyl + Thiaz n=13 Participants Eligible participants received a single subcutaneous injection of Placebo to Canakinumab. Patients must have had documented diagnosis of Type 2 Diabetes Mellitus and be on a stable dose of Metformin (Met) at least 1000 mg/day , and a Sulfonylurea (Sulfonyl), at least 1/2 the maximally labeled dose, and a Thiazolidinedione (Thiaz)at least 1/2 the maximally labeled dose combination therapy, for 3 months prior to screening.	Canakinumab 150 mg + Insulin n=25 Participants Eligible participants received a single subcutaneous injection of Canakinumab 150 mg. Patients must have had documented diagnosis of Type 2 Diabetes Mellitus for 3 months prior to screening and be on a stable dose of Insulin, 2 insulin injections per day for a total daily dose of less than 100 U with or without Metformin (Met)for 3 months prior to screening	Placebo + Insulin n=15 Participants Eligible participants received a single subcutaneous injection of Placebo to Canakinumab. Patients must have had documented diagnosis of Type 2 Diabetes Mellitus for 3 months prior to screening and be on a stable dose of Insulin, 2 insulin injections per day for a total daily dose of less than 100 U with or without Metformin (Met)for 3 months prior to screening	Canakinumab 150 mg in Participants With IGT n=26 Participants Eligible participants received a single subcutaneous injection of Canakinumab 150 mg. Patients must have had Impaired Glucose Tolerance (IGT) as defined by the World Health Organization (WHO) criteria confirmed at screening visit.	Placebo in Participants With IGT n=21 Participants Eligible participants received a single subcutaneous injection of Placebo to Canakinumab. Patients must have had Impaired Glucose Tolerance (IGT) as defined by the World Health Organization (WHO) criteria confirmed at screening visit.
Mean Change in Fasting Glucose Disposition Index(GDI)1 and Index 2, From Baseline to 4 Weeks Index 1	0.06 number Standard Error 0.374	-0.29 number Standard Error 0.546	0.06 number Standard Error 0.386	0.37 number Standard Error 0.546	0.24 number Standard Error 0.386	0.33 number Standard Error 0.586	0.25 number Standard Error 0.423	-0.27 number Standard Error 0.546	-0.51 number Standard Error 0.672	-0.64 number Standard Error 0.530
Mean Change in Fasting Glucose Disposition Index(GDI)1 and Index 2, From Baseline to 4 Weeks Index 2 (n= 32,15, 29,15, 30,13, 25, 15, 20, 26)	0.14 number Standard Error 0.652	-0.81 number Standard Error 0.952	-0.94 number Standard Error 0.685	0.81 number Standard Error 0.952	0.62 number Standard Error 0.673	0.49 number Standard Error 1.023	-0.21 number Standard Error 0.738	-0.25 number Standard Error 0.952	-0.16 number Standard Error 0.396	-0.31 number Standard Error 0.509

SECONDARY outcome

Timeframe: Baseline, 4 weeks

Population: Participants from the full analysis set who participated in the meal challenge and who had at least 1 post-baseline absolute glucose measurement at 2 hours.

Change in glucose level measured after 2 hours of fasting. Blood sample was drawn at 0 minutes and at 240 minutes.

A mixed model with treatment fitted as fixed effect, and population and the interaction of population and treatment fitted as random effects were used for the comparison of Canakinumab versus placebo within each T2DM population. The mixed model did not include participants from the IGT population.

Outcome measures

Measure	Canakinumab 150 mg + Metformin n=32 Participants Eligible participants received a single subcutaneous injection Canakinumab 150 mg. Patients must have had documented diagnosis of Type 2 Diabetes Mellitus and be on a stable dose of Metformin (Met) monotherapy treatment at least 1000 mg/day for 3 months prior to screening	Placebo + Metformin n=16 Participants Eligible participants received a single subcutaneous injection of Placebo to Canakinumab. Patients must have had documented diagnosis of Type 2 Diabetes Mellitus and be on a stable dose of Metformin (Met) monotherapy treatment at least 1000 mg/day for 3 months prior to screening	Canakinumab 150 mg + Metformin + Sulfonylurea n=31 Participants Eligible participants received a single subcutaneous injection of Canakinumab 150 mg.Patients must have had documented diagnosis of Type 2 Diabetes Mellitus and be on a stable dose of Metformin (Met) at least 1000 mg/day , and a Sulfonylurea (Sulfonyl), at least 1/2 the maximally labeled dose combination therapy, for 3 months prior to screening.	Placebo + Metformin + Sulfonylurea n=15 Participants Eligible participants received a single subcutaneous injection of Placebo to Canakinumab.Patients must have had documented diagnosis of Type 2 Diabetes Mellitus and be on a stable dose of Metformin (Met) at least 1000 mg/day , and a Sulfonylurea (Sulfonyl), at least 1/2 the maximally labeled dose combination therapy, for 3 months prior to screening.	Canakinumab 150 mg Canakinumab 150 mg + Met + Sulfonyl + Thia n=31 Participants Eligible participants received a single subcutaneous injection of Canakinumab 150 mg.Patients must have had documented diagnosis of Type 2 Diabetes Mellitus and be on a stable dose of Metformin (Met) at least 1000 mg/day , and a Sulfonylurea (Sulfonyl), at least 1/2 the maximally labeled dose, and a Thiazolidinedione (Thiaz)at least 1/2 the maximally labeled dose combination therapy, for 3 months prior to screening.	Placebo + Met + Sulfonyl + Thiaz n=14 Participants Eligible participants received a single subcutaneous injection of Placebo to Canakinumab. Patients must have had documented diagnosis of Type 2 Diabetes Mellitus and be on a stable dose of Metformin (Met) at least 1000 mg/day , and a Sulfonylurea (Sulfonyl), at least 1/2 the maximally labeled dose, and a Thiazolidinedione (Thiaz)at least 1/2 the maximally labeled dose combination therapy, for 3 months prior to screening.	Canakinumab 150 mg + Insulin n=26 Participants Eligible participants received a single subcutaneous injection of Canakinumab 150 mg. Patients must have had documented diagnosis of Type 2 Diabetes Mellitus for 3 months prior to screening and be on a stable dose of Insulin, 2 insulin injections per day for a total daily dose of less than 100 U with or without Metformin (Met)for 3 months prior to screening	Placebo + Insulin n=15 Participants Eligible participants received a single subcutaneous injection of Placebo to Canakinumab. Patients must have had documented diagnosis of Type 2 Diabetes Mellitus for 3 months prior to screening and be on a stable dose of Insulin, 2 insulin injections per day for a total daily dose of less than 100 U with or without Metformin (Met)for 3 months prior to screening	Canakinumab 150 mg in Participants With IGT n=28 Participants Eligible participants received a single subcutaneous injection of Canakinumab 150 mg. Patients must have had Impaired Glucose Tolerance (IGT) as defined by the World Health Organization (WHO) criteria confirmed at screening visit.	Placebo in Participants With IGT n=21 Participants Eligible participants received a single subcutaneous injection of Placebo to Canakinumab. Patients must have had Impaired Glucose Tolerance (IGT) as defined by the World Health Organization (WHO) criteria confirmed at screening visit.
Mean Change in Absolute Glucose Level at 2 Hours, From Baseline to 4 Weeks	-0.53 mmol/L Standard Error 0.389	0.13 mmol/L Standard Error 0.551	-0.60 mmol/L Standard Error 0.396	0.18 mmol/L Standard Error 0.551	-1.08 mmol/L Standard Error 0.396	-0.56 mmol/L Standard Error 0.589	-0.56 mmol/L Standard Error 0.432	-0.16 mmol/L Standard Error 0.569	-0.26 mmol/L Standard Error 0.241	-0.25 mmol/L Standard Error 0.213

SECONDARY outcome

Timeframe: Baseline, 4 weeks

Population: Participants from the full analysis set who participated in the meal challenge and who had at least 1 post-baseline absolute glucose measurement at 2 hours.

Blood samples were drawn after a test meal at 0, 15, 30, 45, 60, 90, 120, 180 and 240 min. Insulin levels over 4 hrs were shown as Area Under the Curve,(AUC). AUC was calculated as: x=1 AUC ΣAx n Where Ax = AUC for the 240 min.interval, and X = 1 for the 1st interval. A mixed model with treatment fitted as fixed effect, and population and the interaction of population and treatment fitted as random effects were used for the comparison of Canakinumab vs placebo within each T2DM group. The mixed model didn't include the IGT group.

Outcome measures

Measure	Canakinumab 150 mg + Metformin n=32 Participants Eligible participants received a single subcutaneous injection Canakinumab 150 mg. Patients must have had documented diagnosis of Type 2 Diabetes Mellitus and be on a stable dose of Metformin (Met) monotherapy treatment at least 1000 mg/day for 3 months prior to screening	Placebo + Metformin n=16 Participants Eligible participants received a single subcutaneous injection of Placebo to Canakinumab. Patients must have had documented diagnosis of Type 2 Diabetes Mellitus and be on a stable dose of Metformin (Met) monotherapy treatment at least 1000 mg/day for 3 months prior to screening	Canakinumab 150 mg + Metformin + Sulfonylurea n=31 Participants Eligible participants received a single subcutaneous injection of Canakinumab 150 mg.Patients must have had documented diagnosis of Type 2 Diabetes Mellitus and be on a stable dose of Metformin (Met) at least 1000 mg/day , and a Sulfonylurea (Sulfonyl), at least 1/2 the maximally labeled dose combination therapy, for 3 months prior to screening.	Placebo + Metformin + Sulfonylurea n=15 Participants Eligible participants received a single subcutaneous injection of Placebo to Canakinumab.Patients must have had documented diagnosis of Type 2 Diabetes Mellitus and be on a stable dose of Metformin (Met) at least 1000 mg/day , and a Sulfonylurea (Sulfonyl), at least 1/2 the maximally labeled dose combination therapy, for 3 months prior to screening.	Canakinumab 150 mg Canakinumab 150 mg + Met + Sulfonyl + Thia n=31 Participants Eligible participants received a single subcutaneous injection of Canakinumab 150 mg.Patients must have had documented diagnosis of Type 2 Diabetes Mellitus and be on a stable dose of Metformin (Met) at least 1000 mg/day , and a Sulfonylurea (Sulfonyl), at least 1/2 the maximally labeled dose, and a Thiazolidinedione (Thiaz)at least 1/2 the maximally labeled dose combination therapy, for 3 months prior to screening.	Placebo + Met + Sulfonyl + Thiaz n=14 Participants Eligible participants received a single subcutaneous injection of Placebo to Canakinumab. Patients must have had documented diagnosis of Type 2 Diabetes Mellitus and be on a stable dose of Metformin (Met) at least 1000 mg/day , and a Sulfonylurea (Sulfonyl), at least 1/2 the maximally labeled dose, and a Thiazolidinedione (Thiaz)at least 1/2 the maximally labeled dose combination therapy, for 3 months prior to screening.	Canakinumab 150 mg + Insulin n=26 Participants Eligible participants received a single subcutaneous injection of Canakinumab 150 mg. Patients must have had documented diagnosis of Type 2 Diabetes Mellitus for 3 months prior to screening and be on a stable dose of Insulin, 2 insulin injections per day for a total daily dose of less than 100 U with or without Metformin (Met)for 3 months prior to screening	Placebo + Insulin n=15 Participants Eligible participants received a single subcutaneous injection of Placebo to Canakinumab. Patients must have had documented diagnosis of Type 2 Diabetes Mellitus for 3 months prior to screening and be on a stable dose of Insulin, 2 insulin injections per day for a total daily dose of less than 100 U with or without Metformin (Met)for 3 months prior to screening	Canakinumab 150 mg in Participants With IGT n=28 Participants Eligible participants received a single subcutaneous injection of Canakinumab 150 mg. Patients must have had Impaired Glucose Tolerance (IGT) as defined by the World Health Organization (WHO) criteria confirmed at screening visit.	Placebo in Participants With IGT n=21 Participants Eligible participants received a single subcutaneous injection of Placebo to Canakinumab. Patients must have had Impaired Glucose Tolerance (IGT) as defined by the World Health Organization (WHO) criteria confirmed at screening visit.
Mean Change in Insulin Area Under the Curve (AUC) 0-4 Hours, From Baseline to 4 Weeks	-9.37 pmol*hour/L Standard Error 40.538	1.21 pmol*hour/L Standard Error 60.128	-73.25 pmol*hour/L Standard Error 42.517	-38.32 pmol*hour/L Standard Error 60.128	-36.96 pmol*hour/L Standard Error 41.825	8.46 pmol*hour/L Standard Error 64.587	163.87 pmol*hour/L Standard Error 45.670	139.24 pmol*hour/L Standard Error 60.128	44.27 pmol*hour/L Standard Error 60.700	-106.68 pmol*hour/L Standard Error 53.615

SECONDARY outcome

Timeframe: Baseline, 4 weeks

Population: Participants from the full analysis set who participated in the meal challenge and who had at least 1 post-baseline absolute glucose measurement at 2 hours.

Blood samples were drawn after a test meal at 0, 15, 30, 45, 60, 90, 120, 180 and 240 min. Insulin levels over 4 hrs were shown as Area Under the Curve,(AUC). AUC was calculated as: x=1 AUC ΣAx n Where Ax = AUC for the 240 min.interval, and X = 1 for the 1st interval. A mixed model with treatment fitted as fixed effect, and population and the interaction of population and treatment fitted as random effects were used for the comparison of Canakinumab vs placebo within each T2DM group. The mixed model didn't include the IGT group.

Outcome measures

Measure	Canakinumab 150 mg + Metformin n=32 Participants Eligible participants received a single subcutaneous injection Canakinumab 150 mg. Patients must have had documented diagnosis of Type 2 Diabetes Mellitus and be on a stable dose of Metformin (Met) monotherapy treatment at least 1000 mg/day for 3 months prior to screening	Placebo + Metformin n=16 Participants Eligible participants received a single subcutaneous injection of Placebo to Canakinumab. Patients must have had documented diagnosis of Type 2 Diabetes Mellitus and be on a stable dose of Metformin (Met) monotherapy treatment at least 1000 mg/day for 3 months prior to screening	Canakinumab 150 mg + Metformin + Sulfonylurea n=31 Participants Eligible participants received a single subcutaneous injection of Canakinumab 150 mg.Patients must have had documented diagnosis of Type 2 Diabetes Mellitus and be on a stable dose of Metformin (Met) at least 1000 mg/day , and a Sulfonylurea (Sulfonyl), at least 1/2 the maximally labeled dose combination therapy, for 3 months prior to screening.	Placebo + Metformin + Sulfonylurea n=15 Participants Eligible participants received a single subcutaneous injection of Placebo to Canakinumab.Patients must have had documented diagnosis of Type 2 Diabetes Mellitus and be on a stable dose of Metformin (Met) at least 1000 mg/day , and a Sulfonylurea (Sulfonyl), at least 1/2 the maximally labeled dose combination therapy, for 3 months prior to screening.	Canakinumab 150 mg Canakinumab 150 mg + Met + Sulfonyl + Thia n=31 Participants Eligible participants received a single subcutaneous injection of Canakinumab 150 mg.Patients must have had documented diagnosis of Type 2 Diabetes Mellitus and be on a stable dose of Metformin (Met) at least 1000 mg/day , and a Sulfonylurea (Sulfonyl), at least 1/2 the maximally labeled dose, and a Thiazolidinedione (Thiaz)at least 1/2 the maximally labeled dose combination therapy, for 3 months prior to screening.	Placebo + Met + Sulfonyl + Thiaz n=14 Participants Eligible participants received a single subcutaneous injection of Placebo to Canakinumab. Patients must have had documented diagnosis of Type 2 Diabetes Mellitus and be on a stable dose of Metformin (Met) at least 1000 mg/day , and a Sulfonylurea (Sulfonyl), at least 1/2 the maximally labeled dose, and a Thiazolidinedione (Thiaz)at least 1/2 the maximally labeled dose combination therapy, for 3 months prior to screening.	Canakinumab 150 mg + Insulin n=26 Participants Eligible participants received a single subcutaneous injection of Canakinumab 150 mg. Patients must have had documented diagnosis of Type 2 Diabetes Mellitus for 3 months prior to screening and be on a stable dose of Insulin, 2 insulin injections per day for a total daily dose of less than 100 U with or without Metformin (Met)for 3 months prior to screening	Placebo + Insulin n=15 Participants Eligible participants received a single subcutaneous injection of Placebo to Canakinumab. Patients must have had documented diagnosis of Type 2 Diabetes Mellitus for 3 months prior to screening and be on a stable dose of Insulin, 2 insulin injections per day for a total daily dose of less than 100 U with or without Metformin (Met)for 3 months prior to screening	Canakinumab 150 mg in Participants With IGT n=28 Participants Eligible participants received a single subcutaneous injection of Canakinumab 150 mg. Patients must have had Impaired Glucose Tolerance (IGT) as defined by the World Health Organization (WHO) criteria confirmed at screening visit.	Placebo in Participants With IGT n=21 Participants Eligible participants received a single subcutaneous injection of Placebo to Canakinumab. Patients must have had Impaired Glucose Tolerance (IGT) as defined by the World Health Organization (WHO) criteria confirmed at screening visit.
Mean Change in C-peptide Area Under the Curve (AUC), 0-4 Hours, From Baseline to 4 Weeks	-0.18 nmol*hour/L Standard Error 0.225	-0.18 nmol*hour/L Standard Error 0.324	-0.21 nmol*hour/L Standard Error 0.232	0.12 nmol*hour/L Standard Error 0.334	-0.61 nmol*hour/L Standard Error 0.229	0.02 nmol*hour/L Standard Error 0.346	0.16 nmol*hour/L Standard Error 0.249	-0.29 nmol*hour/L Standard Error 0.334	-0.43 nmol*hour/L Standard Error 0.253	-0.40 nmol*hour/L Standard Error 0.288

SECONDARY outcome

Timeframe: Baseline, 4 weeks

Population: Participants from the full analysis set who participated in the meal challenge and who had at least 1 post-baseline absolute glucose measurement at 2 hours.

Blood samples were drawn after a test meal at 0, 15, 30, 45, 60, 90, 120, 180 and 240 min. Insulin levels over 4 hrs were shown as Area Under the Curve,(AUC). AUC was calculated as: x=1 AUC ΣAx n Where Ax = AUC for the 240 min.interval, and X = 1 for the 1st interval. A mixed model with treatment fitted as fixed effect, and population and the interaction of population and treatment fitted as random effects were used for the comparison of Canakinumab vs placebo within each T2DM group. The mixed model didn't include the IGT group.

Outcome measures

Measure	Canakinumab 150 mg + Metformin n=32 Participants Eligible participants received a single subcutaneous injection Canakinumab 150 mg. Patients must have had documented diagnosis of Type 2 Diabetes Mellitus and be on a stable dose of Metformin (Met) monotherapy treatment at least 1000 mg/day for 3 months prior to screening	Placebo + Metformin n=16 Participants Eligible participants received a single subcutaneous injection of Placebo to Canakinumab. Patients must have had documented diagnosis of Type 2 Diabetes Mellitus and be on a stable dose of Metformin (Met) monotherapy treatment at least 1000 mg/day for 3 months prior to screening	Canakinumab 150 mg + Metformin + Sulfonylurea n=31 Participants Eligible participants received a single subcutaneous injection of Canakinumab 150 mg.Patients must have had documented diagnosis of Type 2 Diabetes Mellitus and be on a stable dose of Metformin (Met) at least 1000 mg/day , and a Sulfonylurea (Sulfonyl), at least 1/2 the maximally labeled dose combination therapy, for 3 months prior to screening.	Placebo + Metformin + Sulfonylurea n=15 Participants Eligible participants received a single subcutaneous injection of Placebo to Canakinumab.Patients must have had documented diagnosis of Type 2 Diabetes Mellitus and be on a stable dose of Metformin (Met) at least 1000 mg/day , and a Sulfonylurea (Sulfonyl), at least 1/2 the maximally labeled dose combination therapy, for 3 months prior to screening.	Canakinumab 150 mg Canakinumab 150 mg + Met + Sulfonyl + Thia n=31 Participants Eligible participants received a single subcutaneous injection of Canakinumab 150 mg.Patients must have had documented diagnosis of Type 2 Diabetes Mellitus and be on a stable dose of Metformin (Met) at least 1000 mg/day , and a Sulfonylurea (Sulfonyl), at least 1/2 the maximally labeled dose, and a Thiazolidinedione (Thiaz)at least 1/2 the maximally labeled dose combination therapy, for 3 months prior to screening.	Placebo + Met + Sulfonyl + Thiaz n=14 Participants Eligible participants received a single subcutaneous injection of Placebo to Canakinumab. Patients must have had documented diagnosis of Type 2 Diabetes Mellitus and be on a stable dose of Metformin (Met) at least 1000 mg/day , and a Sulfonylurea (Sulfonyl), at least 1/2 the maximally labeled dose, and a Thiazolidinedione (Thiaz)at least 1/2 the maximally labeled dose combination therapy, for 3 months prior to screening.	Canakinumab 150 mg + Insulin n=26 Participants Eligible participants received a single subcutaneous injection of Canakinumab 150 mg. Patients must have had documented diagnosis of Type 2 Diabetes Mellitus for 3 months prior to screening and be on a stable dose of Insulin, 2 insulin injections per day for a total daily dose of less than 100 U with or without Metformin (Met)for 3 months prior to screening	Placebo + Insulin n=15 Participants Eligible participants received a single subcutaneous injection of Placebo to Canakinumab. Patients must have had documented diagnosis of Type 2 Diabetes Mellitus for 3 months prior to screening and be on a stable dose of Insulin, 2 insulin injections per day for a total daily dose of less than 100 U with or without Metformin (Met)for 3 months prior to screening	Canakinumab 150 mg in Participants With IGT n=28 Participants Eligible participants received a single subcutaneous injection of Canakinumab 150 mg. Patients must have had Impaired Glucose Tolerance (IGT) as defined by the World Health Organization (WHO) criteria confirmed at screening visit.	Placebo in Participants With IGT n=21 Participants Eligible participants received a single subcutaneous injection of Placebo to Canakinumab. Patients must have had Impaired Glucose Tolerance (IGT) as defined by the World Health Organization (WHO) criteria confirmed at screening visit.
Mean Change in Post-prandial Glucose Area Under the Curve (AUC)0-4 Hours, From Baseline to 4 Weeks	-0.59 mmol*hr/L Standard Error 1.296	0.46 mmol*hr/L Standard Error 1.861	-1.37 mmol*hr/L Standard Error 1.337	-1.24 mmol*hr/L Standard Error 1.861	-3.58 mmol*hr/L Standard Error 1.316	-2.88 mmol*hr/L Standard Error 1.990	-1.49 mmol*hr/L Standard Error 1.460	-1.76 mmol*hr/L Standard Error 1.922	-0.71 mmol*hr/L Standard Error 0.554	-0.10 mmol*hr/L Standard Error 0.512

SECONDARY outcome

Timeframe: Baseline, 4 weeks

Population: Participants from the full analysis set who participated in the meal challenge and who had at least 1 post-baseline absolute glucose measurement at 2 hours.

Change in peak plasma glucose level as measured from Baseline to 4 weeks of treatment.

A mixed model with treatment fitted as fixed effect, and population and the interaction of population and treatment fitted as random effects were used for the comparison of Canakinumab versus placebo within each T2DM population. The mixed model did not include participants from the IGT population.

Outcome measures

Measure	Canakinumab 150 mg + Metformin n=32 Participants Eligible participants received a single subcutaneous injection Canakinumab 150 mg. Patients must have had documented diagnosis of Type 2 Diabetes Mellitus and be on a stable dose of Metformin (Met) monotherapy treatment at least 1000 mg/day for 3 months prior to screening	Placebo + Metformin n=16 Participants Eligible participants received a single subcutaneous injection of Placebo to Canakinumab. Patients must have had documented diagnosis of Type 2 Diabetes Mellitus and be on a stable dose of Metformin (Met) monotherapy treatment at least 1000 mg/day for 3 months prior to screening	Canakinumab 150 mg + Metformin + Sulfonylurea n=31 Participants Eligible participants received a single subcutaneous injection of Canakinumab 150 mg.Patients must have had documented diagnosis of Type 2 Diabetes Mellitus and be on a stable dose of Metformin (Met) at least 1000 mg/day , and a Sulfonylurea (Sulfonyl), at least 1/2 the maximally labeled dose combination therapy, for 3 months prior to screening.	Placebo + Metformin + Sulfonylurea n=15 Participants Eligible participants received a single subcutaneous injection of Placebo to Canakinumab.Patients must have had documented diagnosis of Type 2 Diabetes Mellitus and be on a stable dose of Metformin (Met) at least 1000 mg/day , and a Sulfonylurea (Sulfonyl), at least 1/2 the maximally labeled dose combination therapy, for 3 months prior to screening.	Canakinumab 150 mg Canakinumab 150 mg + Met + Sulfonyl + Thia n=31 Participants Eligible participants received a single subcutaneous injection of Canakinumab 150 mg.Patients must have had documented diagnosis of Type 2 Diabetes Mellitus and be on a stable dose of Metformin (Met) at least 1000 mg/day , and a Sulfonylurea (Sulfonyl), at least 1/2 the maximally labeled dose, and a Thiazolidinedione (Thiaz)at least 1/2 the maximally labeled dose combination therapy, for 3 months prior to screening.	Placebo + Met + Sulfonyl + Thiaz n=14 Participants Eligible participants received a single subcutaneous injection of Placebo to Canakinumab. Patients must have had documented diagnosis of Type 2 Diabetes Mellitus and be on a stable dose of Metformin (Met) at least 1000 mg/day , and a Sulfonylurea (Sulfonyl), at least 1/2 the maximally labeled dose, and a Thiazolidinedione (Thiaz)at least 1/2 the maximally labeled dose combination therapy, for 3 months prior to screening.	Canakinumab 150 mg + Insulin n=26 Participants Eligible participants received a single subcutaneous injection of Canakinumab 150 mg. Patients must have had documented diagnosis of Type 2 Diabetes Mellitus for 3 months prior to screening and be on a stable dose of Insulin, 2 insulin injections per day for a total daily dose of less than 100 U with or without Metformin (Met)for 3 months prior to screening	Placebo + Insulin n=15 Participants Eligible participants received a single subcutaneous injection of Placebo to Canakinumab. Patients must have had documented diagnosis of Type 2 Diabetes Mellitus for 3 months prior to screening and be on a stable dose of Insulin, 2 insulin injections per day for a total daily dose of less than 100 U with or without Metformin (Met)for 3 months prior to screening	Canakinumab 150 mg in Participants With IGT n=28 Participants Eligible participants received a single subcutaneous injection of Canakinumab 150 mg. Patients must have had Impaired Glucose Tolerance (IGT) as defined by the World Health Organization (WHO) criteria confirmed at screening visit.	Placebo in Participants With IGT n=21 Participants Eligible participants received a single subcutaneous injection of Placebo to Canakinumab. Patients must have had Impaired Glucose Tolerance (IGT) as defined by the World Health Organization (WHO) criteria confirmed at screening visit.
Mean Change in Peak Plasma Glucose, From Baseline to 4 Weeks	-0.41 mmol/L Standard Error 0.369	0.21 mmol/L Standard Error 0.531	-0.43 mmol/L Standard Error 0.381	-0.03 mmol/L Standard Error 0.531	-0.82 mmol/L Standard Error 0.375	-0.77 mmol/L Standard Error 0.567	-0.15 mmol/L Standard Error 0.416	-0.60 mmol/L Standard Error 0.548	-0.34 mmol/L Standard Error 0.181	-0.04 mmol/L Standard Error 0.189

SECONDARY outcome

Timeframe: Baseline, 4 weeks

Population: Participants from the full analysis set who participated in the meal challenge and who had at least 1 post-baseline absolute glucose measurement at 2 hours.

Change in mean peak plasma Insulin level as measured from Baseline to 4 weeks of treatment. A mixed model with treatment fitted as fixed effect, and population and the interaction of population and treatment fitted as random effects were used for the comparison of Canakinumab versus placebo within each T2DM population. The mixed model did not include participants from the IGT population.

Outcome measures

Measure	Canakinumab 150 mg + Metformin n=32 Participants Eligible participants received a single subcutaneous injection Canakinumab 150 mg. Patients must have had documented diagnosis of Type 2 Diabetes Mellitus and be on a stable dose of Metformin (Met) monotherapy treatment at least 1000 mg/day for 3 months prior to screening	Placebo + Metformin n=16 Participants Eligible participants received a single subcutaneous injection of Placebo to Canakinumab. Patients must have had documented diagnosis of Type 2 Diabetes Mellitus and be on a stable dose of Metformin (Met) monotherapy treatment at least 1000 mg/day for 3 months prior to screening	Canakinumab 150 mg + Metformin + Sulfonylurea n=31 Participants Eligible participants received a single subcutaneous injection of Canakinumab 150 mg.Patients must have had documented diagnosis of Type 2 Diabetes Mellitus and be on a stable dose of Metformin (Met) at least 1000 mg/day , and a Sulfonylurea (Sulfonyl), at least 1/2 the maximally labeled dose combination therapy, for 3 months prior to screening.	Placebo + Metformin + Sulfonylurea n=15 Participants Eligible participants received a single subcutaneous injection of Placebo to Canakinumab.Patients must have had documented diagnosis of Type 2 Diabetes Mellitus and be on a stable dose of Metformin (Met) at least 1000 mg/day , and a Sulfonylurea (Sulfonyl), at least 1/2 the maximally labeled dose combination therapy, for 3 months prior to screening.	Canakinumab 150 mg Canakinumab 150 mg + Met + Sulfonyl + Thia n=31 Participants Eligible participants received a single subcutaneous injection of Canakinumab 150 mg.Patients must have had documented diagnosis of Type 2 Diabetes Mellitus and be on a stable dose of Metformin (Met) at least 1000 mg/day , and a Sulfonylurea (Sulfonyl), at least 1/2 the maximally labeled dose, and a Thiazolidinedione (Thiaz)at least 1/2 the maximally labeled dose combination therapy, for 3 months prior to screening.	Placebo + Met + Sulfonyl + Thiaz n=14 Participants Eligible participants received a single subcutaneous injection of Placebo to Canakinumab. Patients must have had documented diagnosis of Type 2 Diabetes Mellitus and be on a stable dose of Metformin (Met) at least 1000 mg/day , and a Sulfonylurea (Sulfonyl), at least 1/2 the maximally labeled dose, and a Thiazolidinedione (Thiaz)at least 1/2 the maximally labeled dose combination therapy, for 3 months prior to screening.	Canakinumab 150 mg + Insulin n=26 Participants Eligible participants received a single subcutaneous injection of Canakinumab 150 mg. Patients must have had documented diagnosis of Type 2 Diabetes Mellitus for 3 months prior to screening and be on a stable dose of Insulin, 2 insulin injections per day for a total daily dose of less than 100 U with or without Metformin (Met)for 3 months prior to screening	Placebo + Insulin n=15 Participants Eligible participants received a single subcutaneous injection of Placebo to Canakinumab. Patients must have had documented diagnosis of Type 2 Diabetes Mellitus for 3 months prior to screening and be on a stable dose of Insulin, 2 insulin injections per day for a total daily dose of less than 100 U with or without Metformin (Met)for 3 months prior to screening	Canakinumab 150 mg in Participants With IGT n=28 Participants Eligible participants received a single subcutaneous injection of Canakinumab 150 mg. Patients must have had Impaired Glucose Tolerance (IGT) as defined by the World Health Organization (WHO) criteria confirmed at screening visit.	Placebo in Participants With IGT n=21 Participants Eligible participants received a single subcutaneous injection of Placebo to Canakinumab. Patients must have had Impaired Glucose Tolerance (IGT) as defined by the World Health Organization (WHO) criteria confirmed at screening visit.
Mean Change in Peak Plasma Insulin, From Baseline to 4 Weeks	8.09 pmol/L Standard Error 22.673	44.56 pmol/L Standard Error 32.561	-55.07 pmol/L Standard Error 23.779	11.33 pmol/L Standard Error 33.629	5.13 pmol/L Standard Error 23.392	-5.15 pmol/L Standard Error 36.123	91.74 pmol/L Standard Error 25.065	36.87 pmol/L Standard Error 33.629	56.21 pmol/L Standard Error 27.952	-26.43 pmol/L Standard Error 40.163

SECONDARY outcome

Timeframe: Baseline, 4 weeks

Population: Participants from the full analysis set who participated in the meal challenge and who had at least 1 post-baseline absolute glucose measurement at 2 hours.

Change in mean peak plasma C-peptide level measured from Baseline to 4 weeks of treatment.

A mixed model with treatment fitted as fixed effect, and population and the interaction of population and treatment fitted as random effects were used for the comparison of Canakinumab versus placebo within each T2DM population. The mixed model did not include participants from the IGT population.

Outcome measures

Measure	Canakinumab 150 mg + Metformin n=32 Participants Eligible participants received a single subcutaneous injection Canakinumab 150 mg. Patients must have had documented diagnosis of Type 2 Diabetes Mellitus and be on a stable dose of Metformin (Met) monotherapy treatment at least 1000 mg/day for 3 months prior to screening	Placebo + Metformin n=16 Participants Eligible participants received a single subcutaneous injection of Placebo to Canakinumab. Patients must have had documented diagnosis of Type 2 Diabetes Mellitus and be on a stable dose of Metformin (Met) monotherapy treatment at least 1000 mg/day for 3 months prior to screening	Canakinumab 150 mg + Metformin + Sulfonylurea n=31 Participants Eligible participants received a single subcutaneous injection of Canakinumab 150 mg.Patients must have had documented diagnosis of Type 2 Diabetes Mellitus and be on a stable dose of Metformin (Met) at least 1000 mg/day , and a Sulfonylurea (Sulfonyl), at least 1/2 the maximally labeled dose combination therapy, for 3 months prior to screening.	Placebo + Metformin + Sulfonylurea n=15 Participants Eligible participants received a single subcutaneous injection of Placebo to Canakinumab.Patients must have had documented diagnosis of Type 2 Diabetes Mellitus and be on a stable dose of Metformin (Met) at least 1000 mg/day , and a Sulfonylurea (Sulfonyl), at least 1/2 the maximally labeled dose combination therapy, for 3 months prior to screening.	Canakinumab 150 mg Canakinumab 150 mg + Met + Sulfonyl + Thia n=31 Participants Eligible participants received a single subcutaneous injection of Canakinumab 150 mg.Patients must have had documented diagnosis of Type 2 Diabetes Mellitus and be on a stable dose of Metformin (Met) at least 1000 mg/day , and a Sulfonylurea (Sulfonyl), at least 1/2 the maximally labeled dose, and a Thiazolidinedione (Thiaz)at least 1/2 the maximally labeled dose combination therapy, for 3 months prior to screening.	Placebo + Met + Sulfonyl + Thiaz n=14 Participants Eligible participants received a single subcutaneous injection of Placebo to Canakinumab. Patients must have had documented diagnosis of Type 2 Diabetes Mellitus and be on a stable dose of Metformin (Met) at least 1000 mg/day , and a Sulfonylurea (Sulfonyl), at least 1/2 the maximally labeled dose, and a Thiazolidinedione (Thiaz)at least 1/2 the maximally labeled dose combination therapy, for 3 months prior to screening.	Canakinumab 150 mg + Insulin n=26 Participants Eligible participants received a single subcutaneous injection of Canakinumab 150 mg. Patients must have had documented diagnosis of Type 2 Diabetes Mellitus for 3 months prior to screening and be on a stable dose of Insulin, 2 insulin injections per day for a total daily dose of less than 100 U with or without Metformin (Met)for 3 months prior to screening	Placebo + Insulin n=15 Participants Eligible participants received a single subcutaneous injection of Placebo to Canakinumab. Patients must have had documented diagnosis of Type 2 Diabetes Mellitus for 3 months prior to screening and be on a stable dose of Insulin, 2 insulin injections per day for a total daily dose of less than 100 U with or without Metformin (Met)for 3 months prior to screening	Canakinumab 150 mg in Participants With IGT n=28 Participants Eligible participants received a single subcutaneous injection of Canakinumab 150 mg. Patients must have had Impaired Glucose Tolerance (IGT) as defined by the World Health Organization (WHO) criteria confirmed at screening visit.	Placebo in Participants With IGT n=21 Participants Eligible participants received a single subcutaneous injection of Placebo to Canakinumab. Patients must have had Impaired Glucose Tolerance (IGT) as defined by the World Health Organization (WHO) criteria confirmed at screening visit.
Mean Change in Peak Plasma C-peptide Level, From Baseline to 4 Weeks	-0.04 nmol/L Standard Error 0.081	-0.04 nmol/L Standard Error 0.116	-0.10 nmol/L Standard Error 0.083	0.16 nmol/L Standard Error 0.120	-0.21 nmol/L Standard Error 0.082	0.05 nmol/L Standard Error 0.124	0.07 nmol/L Standard Error 0.089	-0.14 nmol/L Standard Error 0.120	-0.18 nmol/L Standard Error 0.101	-0.18 nmol/L Standard Error 0.134

SECONDARY outcome

Timeframe: Baseline, 4 weeks

Population: Safety Population consisted of all participants who received at least one dose of study medication and had at least one post-baseline safety assessment.

An adverse event is any unwanted event, whether related to study drug or not occuring during the study period. A Serious Adverse Event (SAE) is an event resulting in death, requiring or prolonging hospitalization, a congenital anomaly or other important medical event. AEs and SAEs were recorded at each visit.

Outcome measures

Measure	Canakinumab 150 mg + Metformin n=33 Participants Eligible participants received a single subcutaneous injection Canakinumab 150 mg. Patients must have had documented diagnosis of Type 2 Diabetes Mellitus and be on a stable dose of Metformin (Met) monotherapy treatment at least 1000 mg/day for 3 months prior to screening	Placebo + Metformin n=17 Participants Eligible participants received a single subcutaneous injection of Placebo to Canakinumab. Patients must have had documented diagnosis of Type 2 Diabetes Mellitus and be on a stable dose of Metformin (Met) monotherapy treatment at least 1000 mg/day for 3 months prior to screening	Canakinumab 150 mg + Metformin + Sulfonylurea n=32 Participants Eligible participants received a single subcutaneous injection of Canakinumab 150 mg.Patients must have had documented diagnosis of Type 2 Diabetes Mellitus and be on a stable dose of Metformin (Met) at least 1000 mg/day , and a Sulfonylurea (Sulfonyl), at least 1/2 the maximally labeled dose combination therapy, for 3 months prior to screening.	Placebo + Metformin + Sulfonylurea n=17 Participants Eligible participants received a single subcutaneous injection of Placebo to Canakinumab.Patients must have had documented diagnosis of Type 2 Diabetes Mellitus and be on a stable dose of Metformin (Met) at least 1000 mg/day , and a Sulfonylurea (Sulfonyl), at least 1/2 the maximally labeled dose combination therapy, for 3 months prior to screening.	Canakinumab 150 mg Canakinumab 150 mg + Met + Sulfonyl + Thia n=32 Participants Eligible participants received a single subcutaneous injection of Canakinumab 150 mg.Patients must have had documented diagnosis of Type 2 Diabetes Mellitus and be on a stable dose of Metformin (Met) at least 1000 mg/day , and a Sulfonylurea (Sulfonyl), at least 1/2 the maximally labeled dose, and a Thiazolidinedione (Thiaz)at least 1/2 the maximally labeled dose combination therapy, for 3 months prior to screening.	Placebo + Met + Sulfonyl + Thiaz n=16 Participants Eligible participants received a single subcutaneous injection of Placebo to Canakinumab. Patients must have had documented diagnosis of Type 2 Diabetes Mellitus and be on a stable dose of Metformin (Met) at least 1000 mg/day , and a Sulfonylurea (Sulfonyl), at least 1/2 the maximally labeled dose, and a Thiazolidinedione (Thiaz)at least 1/2 the maximally labeled dose combination therapy, for 3 months prior to screening.	Canakinumab 150 mg + Insulin n=28 Participants Eligible participants received a single subcutaneous injection of Canakinumab 150 mg. Patients must have had documented diagnosis of Type 2 Diabetes Mellitus for 3 months prior to screening and be on a stable dose of Insulin, 2 insulin injections per day for a total daily dose of less than 100 U with or without Metformin (Met)for 3 months prior to screening	Placebo + Insulin n=15 Participants Eligible participants received a single subcutaneous injection of Placebo to Canakinumab. Patients must have had documented diagnosis of Type 2 Diabetes Mellitus for 3 months prior to screening and be on a stable dose of Insulin, 2 insulin injections per day for a total daily dose of less than 100 U with or without Metformin (Met)for 3 months prior to screening	Canakinumab 150 mg in Participants With IGT n=28 Participants Eligible participants received a single subcutaneous injection of Canakinumab 150 mg. Patients must have had Impaired Glucose Tolerance (IGT) as defined by the World Health Organization (WHO) criteria confirmed at screening visit.	Placebo in Participants With IGT n=26 Participants Eligible participants received a single subcutaneous injection of Placebo to Canakinumab. Patients must have had Impaired Glucose Tolerance (IGT) as defined by the World Health Organization (WHO) criteria confirmed at screening visit.
Number of Participants Reporting Death, Serious Adverse Events (SAEs) and Adverse Events (AEs) Above 5% Frequency, From Baseline to 4 Weeks Number of Participants with Serious Adverse Events	0 participants	0 participants	0 participants	0 participants	0 participants	0 participants	0 participants	0 participants	0 participants	0 participants
Number of Participants Reporting Death, Serious Adverse Events (SAEs) and Adverse Events (AEs) Above 5% Frequency, From Baseline to 4 Weeks Number of Participants with Non-serious AEs > 5%	0 participants	4 participants	6 participants	3 participants	4 participants	3 participants	6 participants	3 participants	0 participants	0 participants

Adverse Events

Canakinumab 150 mg + Metformin

Serious events: 0 serious events

Other events: 0 other events

Deaths: 0 deaths

Placebo + Metformin

Serious events: 0 serious events

Other events: 4 other events

Deaths: 0 deaths

Canakinumab 150 mg + Metforimin + Sulfonylurea

Serious events: 0 serious events

Other events: 6 other events

Deaths: 0 deaths

Placebo + Metforimin + Sulfonylurea

Serious events: 0 serious events

Other events: 3 other events

Deaths: 0 deaths

Canakinumab 150 mg + Met + Sulfonyl + Thiazolidinedione

Serious events: 0 serious events

Other events: 4 other events

Deaths: 0 deaths

Placebo + Met + Sulfonyl + Thiazolidinedione

Serious events: 0 serious events

Other events: 3 other events

Deaths: 0 deaths

Canakinumab 150 mg + Insulin

Serious events: 0 serious events

Other events: 6 other events

Deaths: 0 deaths

Placebo + Insulin

Serious events: 0 serious events

Other events: 3 other events

Deaths: 0 deaths

Canakinumab 150 mg in Patients With IGT

Serious events: 0 serious events

Other events: 0 other events

Deaths: 0 deaths

Placebo in Patients With IGT

Serious events: 0 serious events

Other events: 0 other events

Deaths: 0 deaths

Serious adverse events

Adverse event data not reported

Other adverse events

Measure	Canakinumab 150 mg + Metformin n=33 participants at risk Eligible participants received a single subcutaneous injection Canakinumab 150 mg.Patients must have had documented diagnosis of Type 2 Diabetes Mellitus and be on a stable dose of Metformin (Met) monotherapy treatment at least 1000 mg/day for 3 months prior to screening	Placebo + Metformin n=17 participants at risk Eligible participants received a single subcutaneous injection of Placebo to Canakinumab. Patients must have had documented diagnosis of Type 2 Diabetes Mellitus and be on a stable dose of Metformin (Met) monotherapy treatment at least 1000 mg/day for 3 months prior to screening	Canakinumab 150 mg + Metforimin + Sulfonylurea n=32 participants at risk Eligible participants received a single subcutaneous injection of Canakinumab 150 mg.Patients must have had documented diagnosis of Type 2 Diabetes Mellitus and be on a stable dose of Metformin (Met) at least 1000 mg/day , and a Sulfonylurea (Sulfonyl), at least 1/2 the maximally labeled dose combination therapy, for 3 months prior to screening.	Placebo + Metforimin + Sulfonylurea n=17 participants at risk Eligible participants received a single subcutaneous injection of Placebo to Canakinumab.Patients must have had documented diagnosis of Type 2 Diabetes Mellitus and be on a stable dose of Metformin (Met) at least 1000 mg/day , and a Sulfonylurea (Sulfonyl), at least 1/2 the maximally labeled dose combination therapy, for 3 months prior to screening.	Canakinumab 150 mg + Met + Sulfonyl + Thiazolidinedione n=32 participants at risk Eligible participants received a single subcutaneous injection of Canakinumab 150 mg.Patients must have had documented diagnosis of Type 2 Diabetes Mellitus and be on a stable dose of Metformin (Met) at least 1000 mg/day , and a Sulfonylurea (Sulfonyl), at least 1/2 the maximally labeled dose, and a Thiazolidinedione (Thiaz)at least 1/2 the maximally labeled dose combination therapy, for 3 months prior to screening.	Placebo + Met + Sulfonyl + Thiazolidinedione n=16 participants at risk Eligible participants received a single subcutaneous injection of Placebo to Canakinumab. Patients must have had documented diagnosis of Type 2 Diabetes Mellitus and be on a stable dose of Metformin (Met) at least 1000 mg/day , and a Sulfonylurea (Sulfonyl), at least 1/2 the maximally labeled dose, and a Thiazolidinedione (Thiaz)at least 1/2 the maximally labeled dose combination therapy, for 3 months prior to screening.	Canakinumab 150 mg + Insulin n=28 participants at risk Eligible participants received a single subcutaneous injection of Canakinumab 150 mg. Patients must have had documented diagnosis of Type 2 Diabetes Mellitus for 3 months prior to screening and be on a stable dose of Insulin, 2 insulin injections per day for a total daily dose of less than 100 U with or without Metformin (Met)for 3 months prior to screening	Placebo + Insulin n=15 participants at risk Eligible participants received a single subcutaneous injection of Placebo to Canakinumab. Patients must have had documented diagnosis of Type 2 Diabetes Mellitus for 3 months prior to screening and be on a stable dose of Insulin, 2 insulin injections per day for a total daily dose of less than 100 U with or without Metformin (Met)for 3 months prior to screening	Canakinumab 150 mg in Patients With IGT n=28 participants at risk Eligible participants received a single subcutaneous injection of Canakinumab 150 mg. Patients must have had Impaired Glucose Tolerance (IGT) as defined by the World Health Organization (WHO) criteria confirmed at screening visit.	Placebo in Patients With IGT n=26 participants at risk Eligible participants received a single subcutaneous injection of Placebo to Canakinumab. Patients must have had Impaired Glucose Tolerance (IGT) as defined by the World Health Organization (WHO) criteria confirmed at screening visit.
Ear and labyrinth disorders Vertigo	0.00% 0/33 Safety Set included all randomized participants who received study drug.	5.9% 1/17 Safety Set included all randomized participants who received study drug.	0.00% 0/32 Safety Set included all randomized participants who received study drug.	0.00% 0/17 Safety Set included all randomized participants who received study drug.	0.00% 0/32 Safety Set included all randomized participants who received study drug.	0.00% 0/16 Safety Set included all randomized participants who received study drug.	0.00% 0/28 Safety Set included all randomized participants who received study drug.	0.00% 0/15 Safety Set included all randomized participants who received study drug.	0.00% 0/28 Safety Set included all randomized participants who received study drug.	0.00% 0/26 Safety Set included all randomized participants who received study drug.
Eye disorders Vision blurred	0.00% 0/33 Safety Set included all randomized participants who received study drug.	0.00% 0/17 Safety Set included all randomized participants who received study drug.	0.00% 0/32 Safety Set included all randomized participants who received study drug.	0.00% 0/17 Safety Set included all randomized participants who received study drug.	3.1% 1/32 Safety Set included all randomized participants who received study drug.	6.2% 1/16 Safety Set included all randomized participants who received study drug.	0.00% 0/28 Safety Set included all randomized participants who received study drug.	0.00% 0/15 Safety Set included all randomized participants who received study drug.	0.00% 0/28 Safety Set included all randomized participants who received study drug.	0.00% 0/26 Safety Set included all randomized participants who received study drug.
Eye disorders Visual impairment	0.00% 0/33 Safety Set included all randomized participants who received study drug.	0.00% 0/17 Safety Set included all randomized participants who received study drug.	0.00% 0/32 Safety Set included all randomized participants who received study drug.	0.00% 0/17 Safety Set included all randomized participants who received study drug.	0.00% 0/32 Safety Set included all randomized participants who received study drug.	6.2% 1/16 Safety Set included all randomized participants who received study drug.	0.00% 0/28 Safety Set included all randomized participants who received study drug.	0.00% 0/15 Safety Set included all randomized participants who received study drug.	0.00% 0/28 Safety Set included all randomized participants who received study drug.	0.00% 0/26 Safety Set included all randomized participants who received study drug.
Gastrointestinal disorders Diarrhoea	0.00% 0/33 Safety Set included all randomized participants who received study drug.	5.9% 1/17 Safety Set included all randomized participants who received study drug.	3.1% 1/32 Safety Set included all randomized participants who received study drug.	0.00% 0/17 Safety Set included all randomized participants who received study drug.	0.00% 0/32 Safety Set included all randomized participants who received study drug.	0.00% 0/16 Safety Set included all randomized participants who received study drug.	0.00% 0/28 Safety Set included all randomized participants who received study drug.	6.7% 1/15 Safety Set included all randomized participants who received study drug.	0.00% 0/28 Safety Set included all randomized participants who received study drug.	0.00% 0/26 Safety Set included all randomized participants who received study drug.
Gastrointestinal disorders Dyspepsia	0.00% 0/33 Safety Set included all randomized participants who received study drug.	0.00% 0/17 Safety Set included all randomized participants who received study drug.	0.00% 0/32 Safety Set included all randomized participants who received study drug.	0.00% 0/17 Safety Set included all randomized participants who received study drug.	0.00% 0/32 Safety Set included all randomized participants who received study drug.	0.00% 0/16 Safety Set included all randomized participants who received study drug.	0.00% 0/28 Safety Set included all randomized participants who received study drug.	6.7% 1/15 Safety Set included all randomized participants who received study drug.	0.00% 0/28 Safety Set included all randomized participants who received study drug.	0.00% 0/26 Safety Set included all randomized participants who received study drug.
Gastrointestinal disorders Nausea	0.00% 0/33 Safety Set included all randomized participants who received study drug.	0.00% 0/17 Safety Set included all randomized participants who received study drug.	3.1% 1/32 Safety Set included all randomized participants who received study drug.	0.00% 0/17 Safety Set included all randomized participants who received study drug.	0.00% 0/32 Safety Set included all randomized participants who received study drug.	6.2% 1/16 Safety Set included all randomized participants who received study drug.	3.6% 1/28 Safety Set included all randomized participants who received study drug.	0.00% 0/15 Safety Set included all randomized participants who received study drug.	0.00% 0/28 Safety Set included all randomized participants who received study drug.	0.00% 0/26 Safety Set included all randomized participants who received study drug.
Infections and infestations Bronchitis	0.00% 0/33 Safety Set included all randomized participants who received study drug.	0.00% 0/17 Safety Set included all randomized participants who received study drug.	3.1% 1/32 Safety Set included all randomized participants who received study drug.	0.00% 0/17 Safety Set included all randomized participants who received study drug.	0.00% 0/32 Safety Set included all randomized participants who received study drug.	0.00% 0/16 Safety Set included all randomized participants who received study drug.	0.00% 0/28 Safety Set included all randomized participants who received study drug.	6.7% 1/15 Safety Set included all randomized participants who received study drug.	0.00% 0/28 Safety Set included all randomized participants who received study drug.	0.00% 0/26 Safety Set included all randomized participants who received study drug.
Infections and infestations Hordeolum	0.00% 0/33 Safety Set included all randomized participants who received study drug.	5.9% 1/17 Safety Set included all randomized participants who received study drug.	0.00% 0/32 Safety Set included all randomized participants who received study drug.	0.00% 0/17 Safety Set included all randomized participants who received study drug.	0.00% 0/32 Safety Set included all randomized participants who received study drug.	0.00% 0/16 Safety Set included all randomized participants who received study drug.	0.00% 0/28 Safety Set included all randomized participants who received study drug.	0.00% 0/15 Safety Set included all randomized participants who received study drug.	0.00% 0/28 Safety Set included all randomized participants who received study drug.	0.00% 0/26 Safety Set included all randomized participants who received study drug.
Infections and infestations Nasopharyngitis	0.00% 0/33 Safety Set included all randomized participants who received study drug.	11.8% 2/17 Safety Set included all randomized participants who received study drug.	0.00% 0/32 Safety Set included all randomized participants who received study drug.	5.9% 1/17 Safety Set included all randomized participants who received study drug.	0.00% 0/32 Safety Set included all randomized participants who received study drug.	0.00% 0/16 Safety Set included all randomized participants who received study drug.	0.00% 0/28 Safety Set included all randomized participants who received study drug.	0.00% 0/15 Safety Set included all randomized participants who received study drug.	0.00% 0/28 Safety Set included all randomized participants who received study drug.	0.00% 0/26 Safety Set included all randomized participants who received study drug.
Infections and infestations Pharyngitis	0.00% 0/33 Safety Set included all randomized participants who received study drug.	0.00% 0/17 Safety Set included all randomized participants who received study drug.	3.1% 1/32 Safety Set included all randomized participants who received study drug.	5.9% 1/17 Safety Set included all randomized participants who received study drug.	0.00% 0/32 Safety Set included all randomized participants who received study drug.	0.00% 0/16 Safety Set included all randomized participants who received study drug.	0.00% 0/28 Safety Set included all randomized participants who received study drug.	0.00% 0/15 Safety Set included all randomized participants who received study drug.	0.00% 0/28 Safety Set included all randomized participants who received study drug.	0.00% 0/26 Safety Set included all randomized participants who received study drug.
Investigations Antinuclear antibody positive	0.00% 0/33 Safety Set included all randomized participants who received study drug.	5.9% 1/17 Safety Set included all randomized participants who received study drug.	0.00% 0/32 Safety Set included all randomized participants who received study drug.	0.00% 0/17 Safety Set included all randomized participants who received study drug.	0.00% 0/32 Safety Set included all randomized participants who received study drug.	0.00% 0/16 Safety Set included all randomized participants who received study drug.	0.00% 0/28 Safety Set included all randomized participants who received study drug.	0.00% 0/15 Safety Set included all randomized participants who received study drug.	0.00% 0/28 Safety Set included all randomized participants who received study drug.	0.00% 0/26 Safety Set included all randomized participants who received study drug.
Metabolism and nutrition disorders Hypoglycaemia	0.00% 0/33 Safety Set included all randomized participants who received study drug.	0.00% 0/17 Safety Set included all randomized participants who received study drug.	0.00% 0/32 Safety Set included all randomized participants who received study drug.	5.9% 1/17 Safety Set included all randomized participants who received study drug.	0.00% 0/32 Safety Set included all randomized participants who received study drug.	0.00% 0/16 Safety Set included all randomized participants who received study drug.	10.7% 3/28 Safety Set included all randomized participants who received study drug.	0.00% 0/15 Safety Set included all randomized participants who received study drug.	0.00% 0/28 Safety Set included all randomized participants who received study drug.	0.00% 0/26 Safety Set included all randomized participants who received study drug.
Nervous system disorders Dizziness	0.00% 0/33 Safety Set included all randomized participants who received study drug.	0.00% 0/17 Safety Set included all randomized participants who received study drug.	3.1% 1/32 Safety Set included all randomized participants who received study drug.	0.00% 0/17 Safety Set included all randomized participants who received study drug.	6.2% 2/32 Safety Set included all randomized participants who received study drug.	6.2% 1/16 Safety Set included all randomized participants who received study drug.	0.00% 0/28 Safety Set included all randomized participants who received study drug.	0.00% 0/15 Safety Set included all randomized participants who received study drug.	0.00% 0/28 Safety Set included all randomized participants who received study drug.	0.00% 0/26 Safety Set included all randomized participants who received study drug.
Nervous system disorders Tremor	0.00% 0/33 Safety Set included all randomized participants who received study drug.	0.00% 0/17 Safety Set included all randomized participants who received study drug.	3.1% 1/32 Safety Set included all randomized participants who received study drug.	5.9% 1/17 Safety Set included all randomized participants who received study drug.	6.2% 2/32 Safety Set included all randomized participants who received study drug.	0.00% 0/16 Safety Set included all randomized participants who received study drug.	7.1% 2/28 Safety Set included all randomized participants who received study drug.	0.00% 0/15 Safety Set included all randomized participants who received study drug.	0.00% 0/28 Safety Set included all randomized participants who received study drug.	0.00% 0/26 Safety Set included all randomized participants who received study drug.
Psychiatric disorders Confusional state	0.00% 0/33 Safety Set included all randomized participants who received study drug.	0.00% 0/17 Safety Set included all randomized participants who received study drug.	0.00% 0/32 Safety Set included all randomized participants who received study drug.	5.9% 1/17 Safety Set included all randomized participants who received study drug.	0.00% 0/32 Safety Set included all randomized participants who received study drug.	0.00% 0/16 Safety Set included all randomized participants who received study drug.	0.00% 0/28 Safety Set included all randomized participants who received study drug.	0.00% 0/15 Safety Set included all randomized participants who received study drug.	0.00% 0/28 Safety Set included all randomized participants who received study drug.	0.00% 0/26 Safety Set included all randomized participants who received study drug.
Respiratory, thoracic and mediastinal disorders Dysphonia	0.00% 0/33 Safety Set included all randomized participants who received study drug.	0.00% 0/17 Safety Set included all randomized participants who received study drug.	0.00% 0/32 Safety Set included all randomized participants who received study drug.	0.00% 0/17 Safety Set included all randomized participants who received study drug.	0.00% 0/32 Safety Set included all randomized participants who received study drug.	0.00% 0/16 Safety Set included all randomized participants who received study drug.	3.6% 1/28 Safety Set included all randomized participants who received study drug.	6.7% 1/15 Safety Set included all randomized participants who received study drug.	0.00% 0/28 Safety Set included all randomized participants who received study drug.	0.00% 0/26 Safety Set included all randomized participants who received study drug.
Skin and subcutaneous tissue disorders Hyperhidrosis	0.00% 0/33 Safety Set included all randomized participants who received study drug.	0.00% 0/17 Safety Set included all randomized participants who received study drug.	3.1% 1/32 Safety Set included all randomized participants who received study drug.	0.00% 0/17 Safety Set included all randomized participants who received study drug.	6.2% 2/32 Safety Set included all randomized participants who received study drug.	6.2% 1/16 Safety Set included all randomized participants who received study drug.	3.6% 1/28 Safety Set included all randomized participants who received study drug.	0.00% 0/15 Safety Set included all randomized participants who received study drug.	0.00% 0/28 Safety Set included all randomized participants who received study drug.	0.00% 0/26 Safety Set included all randomized participants who received study drug.
Skin and subcutaneous tissue disorders Rash papular	0.00% 0/33 Safety Set included all randomized participants who received study drug.	0.00% 0/17 Safety Set included all randomized participants who received study drug.	0.00% 0/32 Safety Set included all randomized participants who received study drug.	0.00% 0/17 Safety Set included all randomized participants who received study drug.	0.00% 0/32 Safety Set included all randomized participants who received study drug.	0.00% 0/16 Safety Set included all randomized participants who received study drug.	0.00% 0/28 Safety Set included all randomized participants who received study drug.	6.7% 1/15 Safety Set included all randomized participants who received study drug.	0.00% 0/28 Safety Set included all randomized participants who received study drug.	0.00% 0/26 Safety Set included all randomized participants who received study drug.

Additional Information

Dr. Tom Thuren/Global Brand Medical Director

Novartis Pharmaceuticals

Phone: 862-778-1828

Email: tom.thuren@novartis.com

Results disclosure agreements

• Principal investigator is a sponsor employee The terms and conditions of Novartis' agreements with its investigators may vary. However, Novartis does not prohibit any investigator from publishing. Any publications from a single-site are postponed until the publication of the pooled data (i.e., data from all sites) in the clinical trial.
• Publication restrictions are in place

Restriction type: OTHER